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Biological Influences On Sex, Sex Differences & Preferences | Huberman Lab Podcast #14



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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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This podcast is separate from my teaching
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and research roles at Stanford.
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It is, however, part of my desire and effort
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to bring zero cost to consumer information
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about science and science-related tools.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is InsideTracker.
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InsideTracker is a personalized nutrition platform
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that analyzes data from your blood and DNA
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to help you better understand your body
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and help you reach your health goals.
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I'm a big believer in blood tests and DNA tests
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for the simple reason that many of the factors
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that are important for your short-term and long-term health
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and overall wellbeing can only be analyzed
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from blood and DNA tests,
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things like metabolic factors and hormone levels
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really can only be assessed accurately from blood and DNA.
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The thing I like about InsideTracker
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is you don't just get back levels of different hormones
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and metabolic factors and so forth,
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you also get directives.
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It has a dashboard that's very easy to use
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that tells you based on your data
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what sorts of foods you might want to eat more of
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or less of,
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what forms of exercise you might want to do more of
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or less of.
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It's really a wonderful way to assess
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how your behaviors and lifestyle choices
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are interacting with what's going on
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deep within your biology.
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InsideTracker makes all of that super easy to understand.
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It's also really easy to get the blood tests
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and DNA tests taken.
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You can go to a local location
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or they can send somebody to your home if you prefer that.
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If you'd like to try InsideTracker,
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you can visit insidetracker.com slash Huberman
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to get 25% off any of InsideTracker's plans.
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Use the code Huberman at checkout.
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That's insidetracker.com slash Huberman
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to get 25% off any of InsideTracker's plans
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and use the code Huberman at checkout.
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Today's episode is also brought to you by Helix Sleep.
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Helix Sleep makes mattresses and pillows
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that are designed to meet your sleep needs
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in order to optimize your sleep.
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I've done several episodes of this podcast
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and there's a ton of information out there
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pointing to the fact that getting really deep
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restful sleep each night is vital
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for mental and physical health.
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And the mattress that you sleep on and the pillow
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that you use is very important for getting optimal sleep.
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Helix Sleep has a brief two minute quiz that you can take.
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It asks you questions like, do you sleep on your side
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or your back or your stomach, or maybe you don't know,
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do you tend to run hot or cold as you sleep
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or maybe you don't know.
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That two minute quiz matches you to a mattress and pillow
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that's ideal for your sleep needs.
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I took this quiz, I matched to the mattress
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they call the Dusk D-U-S-K
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and I've been sleeping on the Dusk mattress for many months
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now and I've been sleeping better than I ever have before.
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It's really wonderful to have a really good night's sleep
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on a consistent basis, it's a total game changer.
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So if you're interested in upgrading your mattress,
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you can go to helixsleep.com slash Huberman,
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take their two minute sleep quiz
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and they'll match you to a customized mattress
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and you'll get up to $200 off any of their mattress orders
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and two free pillows.
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So that's helixsleep.com slash Huberman,
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take the two minute sleep quiz,
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they'll match you to a mattress
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and if you order one of their mattresses,
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you'll get up to $200 off any of their mattresses
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and two free pillows.
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They have a 10 year warranty
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and you get to try out the mattress
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for a hundred nights risk-free
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and if you don't like it, they'll pick it up
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and take it away.
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If you love it, then you keep it
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and I think there's a very good chance
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that you're going to love it, I certainly love mine.
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And today's episode is also brought to you
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by Athletic Greens.
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Athletic Greens is an all-in-one
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vitamin mineral probiotic drink.
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I started using Athletic Greens way back in 2012
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and so I'm delighted that they're sponsoring the podcast.
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I started using Athletic Greens
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because I found it rather confusing
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to figure out what vitamins and minerals to take.
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And Athletic Greens, I get all the vitamins and minerals
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I need to cover my bases.
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As well, probiotics are really important.
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Probiotics have been shown now in numerous studies
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to be important for the gut microbiome,
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which impacts the gut brain axis
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as well as various aspects of bodily health.
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So in Athletic Greens, I get vitamins,
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minerals and probiotics.
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I also really liked the way it tastes.
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It's a greens drink, so you mix it with some water.
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You could mix it with something else like juice if you like.
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I mix mine with water and lemon juice
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and I drink it once or twice a day.
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If you want to try Athletic Greens,
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you can go to athleticgreens.com slash Huberman.
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And if you do that, you'll claim their special offer,
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which is to get a year supply of vitamin D3K2.
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There's now also a wealth of data
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showing that vitamin D3 is important
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for various aspects of brain and body health.
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So that's athleticgreens.com slash Huberman
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for Athletic Greens and the year supply of vitamin D3K2.
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You'll also get five free travel packets.
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The travel packets are just a really convenient way
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to take Athletic Greens when you're on the road,
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in the car or on a plane, or just moving around.
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You just empty one of the packets into a water bottle
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or a glass and mix it up really quickly.
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It saves any kind of mess or anything of that sort.
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So once again, athleticgreens.com slash Huberman
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to get vitamin D3K2, that's a year supply
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and the five free travel packs.
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It's a new month, which means it's a new topic
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here at the Huberman Lab Podcast.
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For the next four or so episodes,
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we're going to be talking all about hormone effects
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on the brain and body.
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So that's a huge number of different topics.
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We're going to talk about sex.
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We're going to talk about reproduction.
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We're going to talk about puberty a little bit more.
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We talked about that in the previous episode.
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We're going to talk about menopause.
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We're going to talk about birth control.
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We are going to talk about aggression, competition,
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winning, losing.
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Basically, we're going to cover as much about hormones
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as we possibly can in this month.
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And in doing so, we are going to go deep
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into tools and protocols.
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We are also going to talk about a lot of tools
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that relate to things that you might not want to do
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in order to optimize hormone health,
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regardless of stage of life or your goals, et cetera.
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So it's sure to be a month rich with discussion,
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rich with tools, and you're going to learn
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a lot of neuroscience and endocrinology.
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There's actually a field of neuroendocrinology.
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It's actually where I started my graduate work.
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I did a master's in it,
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which is only to say that I love the topic.
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I have a lot of friends that work on this topic,
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many of whom I've consulted for these episodes,
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and I'm really excited to share the information with you.
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Before we dive into today's episode,
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all about emotions and sex,
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I want to just have a few announcements
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that are designed to point you to some useful resources.
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Last episode, talking about the science of emotions
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and relationships, I mentioned the Mood Meter app.
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The Mood Meter app was developed by people out
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at Yale University who study the biology
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and psychology of emotions.
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It's a really wonderful app.
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However, many of you quickly told me
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that the Mood Meter app isn't available in your area.
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You went to the link we posted
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and it just was saying not available in your area.
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The situation was actually a lot worse than that.
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The situation was that when we recorded the episode,
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the Mood Meter app was working.
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I know because I downloaded a fresh copy of it to my phone.
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And then in the ensuing weekend,
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they took the Mood Meter app down for some repairs.
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The Mood Meter app is now up.
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It is available.
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I want to be really clear.
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It's not an app I'm affiliated with.
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I'm just mentioning it to you.
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They don't know me.
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I know them, but they don't know me.
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So we don't have any kind of business relationship.
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They do charge 99 cents for the app.
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I think the free version has disappeared
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in the last year or so.
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So that's Mood Meter app.
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We'll provide the link again
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and the link should be working.
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Hopefully they won't take it down again
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in between this announcement
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and the release of this episode.
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Also just want to take a step back for a moment
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and talk a little bit about the logic
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of how to make the most of the information
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on the Huberman Lab Podcast.
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I tend to throw out a lot of information
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about a given topic.
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Many of you have pointed out, however,
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that I don't cover certain things.
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And once again, I'll just say,
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the goal is always to be accurate,
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but there's no way I can be exhaustive.
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There's no way I can cover everything
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for a particular topic.
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The good news is we have time.
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My goal, at least in the first year
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of the Huberman Lab Podcast,
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is to give you a basis,
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a foundation in these different topics
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of neuroplasticity, focus, sleep, hormones, et cetera.
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And of course, to provide tools along the way.
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We are going to host guests.
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I've actually started recording
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with some of these guests already.
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And even those episodes will include a little,
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what we call primer,
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a little description of the basics of a given topic
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so that you can get more information from those topics.
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My goal really is to educate you in these topics,
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give you a foundation in these topics
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and allow you to start exploring them here in the episodes
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with our future guests,
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but also in other podcasts and books
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and other sources of information.
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So for those of you that are saying
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it's too much information,
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I just encourage you to remind yourself
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that you have a pause button,
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you can return to it, everything's timestamp.
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For those of you who feel it's not enough information,
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I'm not covering enough,
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just know that this is just the beginning.
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We intend to do this for a very long time
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and we will be thorough over time.
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So thanks for your patience.
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And please be patient with yourselves.
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There's no reason why you have to digest
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all the information in one swoop.
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The other thing is that I've been told
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both that I speak too fast and speak too slow.
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So there's a wonderful solution to this.
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If I speak too fast or too slow,
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you can adjust the speed in YouTube.
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If you're listening in a different format,
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I think you also can adjust the speed of playback.
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So that's something that wouldn't be possible
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in the classroom, but you may find useful.
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And then last but not least,
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I want to point people again to this NSDR,
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non-sleep deep rest protocol
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that the folks over at Made For
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have put out as a free resource.
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It does, as many of you pointed out,
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bear resemblance to things like yoga nidra,
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other forms of meditation.
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But what we've done is we've stripped out intentions
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or any kind of the verbiage related
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to what some people might perceive
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as kind of related to the yoga community
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or specific to kind of new agey type techniques,
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not because we don't like yoga nidra.
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In fact, I've done yoga nidra daily
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for almost the last, goodness, eight years of my life.
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I love yoga nidra,
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but sometimes the complicated language can be a separator
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and can discourage people from taking on these protocols
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that are extremely useful.
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So NSDR is intentionally generic.
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It's designed to bring you into a state of deep relaxation
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through a combination of breathing and body scan.
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There's the YouTube script over at Made For,
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which is linked in the caption.
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And many people find that they prefer that
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to scripts like yoga nidra scripts
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where they're doing intentions
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and they're hearing a lot of kind of unusual language
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around the process.
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This is just very basic and I hope you'll enjoy it.
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And if you prefer the more typical yoga nidra scripts,
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then go with those.
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There are many of them available
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on the internet and elsewhere.
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And last but not least,
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I want to point out that all our episodes now
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are subtitled both in English and in Spanish.
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So for those of you that prefer
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to digest this information in Spanish,
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that's now available to you in the subtitles.
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Today, we're going to talk about the science of sex,
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in particular sexual differentiation.
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Now that's a complicated topic
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because sex is both a adjective, a noun, and a verb,
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depending on the context.
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Today, we're going to talk about the hormonal effects
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and the neural effects of particular events
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that happen during development
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and how those guide adolescent and adult behavior,
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including sexual preference.
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It's an area that's fascinating
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and for which there are actually
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very solid textbook findings.
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So textbook findings means that there are many studies
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that have been aggregated over decades
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that point to what we now know to be absolute truths
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in terms of how hormones affect brain development,
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how the brain impacts hormonal development,
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and how those interact to control behavior, for instance.
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We are also going to talk about reproduction, the verb sex.
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And of course, sex, the verb,
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can also be carried out independent of reproduction.
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It's not always in particular in humans
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just to produce offspring.
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So that's going to be covered in the next episode,
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but you absolutely need to understand the information
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in this episode in order to make sense of the information
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in the next episode.
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So today we're going to explore hormones,
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what they are, how they work,
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what leads to masculinization or feminization
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of the brain and body.
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I'll just throw out one really interesting fact
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that perhaps most of you didn't realize
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that hormones have direct effects on the body.
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Most people know that because there are hormone differences
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and sex differences in bodies
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in terms of genitalia and body hair,
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00:13:18.920
distribution of body hair, et cetera.
link |
00:13:21.280
But there are also effects of hormones on the brain directly
link |
00:13:25.140
and believe it or not,
link |
00:13:25.980
there are also effects on the spinal cord,
link |
00:13:28.720
on the neurons and structures within the spinal cord
link |
00:13:31.560
that impact in a very direct way
link |
00:13:33.920
what sorts of behaviors are possible.
link |
00:13:36.620
So it's a fascinating area.
link |
00:13:39.140
You might notice I'm going to go a little bit more slowly
link |
00:13:41.880
through this topic than I normally do.
link |
00:13:43.720
I want to be extremely careful with my language.
link |
00:13:46.700
Some of these topics,
link |
00:13:48.500
some of you may be thinking are extremely sensitive, right?
link |
00:13:51.940
And of course,
link |
00:13:52.880
any discussion about sex and reproduction
link |
00:13:54.960
is a sensitive one,
link |
00:13:56.200
but today we're just talking about the biology.
link |
00:13:58.320
We're not getting into the cultural constraints
link |
00:14:00.240
or the cultural dialogue.
link |
00:14:02.060
What we're trying to do today is really get to the biology,
link |
00:14:06.220
the physiology, the endocrinology and the behavior.
link |
00:14:10.000
So let's start by talking about what hormones are
link |
00:14:14.200
just to remind you and what they do.
link |
00:14:17.040
Hormones by definition are a substance,
link |
00:14:20.000
a chemical that's released in one area of the body,
link |
00:14:22.800
typically from something we call a gland,
link |
00:14:25.000
although they can also be released from neurons,
link |
00:14:28.440
but they're released often from glands
link |
00:14:30.840
that travel and have effects both on that gland,
link |
00:14:35.160
but also on other organs and tissues in the body.
link |
00:14:38.480
And that differentiates hormones
link |
00:14:40.140
from things like neurotransmitters,
link |
00:14:41.880
which tend to act more locally.
link |
00:14:44.160
So that's important.
link |
00:14:45.360
A hormone is a substance secreted at one location,
link |
00:14:47.400
the body travels and has impact
link |
00:14:49.160
on things elsewhere in the body.
link |
00:14:51.640
Examples of tissues that produce hormones
link |
00:14:54.720
would be the thyroid, the testes, the ovaries, et cetera.
link |
00:14:59.160
And then of course there are areas of the brain
link |
00:15:00.780
like the hypothalamus and the pituitary,
link |
00:15:03.880
which are closely related to one another
link |
00:15:06.600
and release hormones that cause the release
link |
00:15:08.680
of yet other hormones out in the body.
link |
00:15:10.320
So we're going to cover all this.
link |
00:15:11.320
If you don't know anything about endocrinology,
link |
00:15:13.360
you're still going to be able to understand
link |
00:15:15.280
today's discussion.
link |
00:15:16.660
And we're going to start with a discussion
link |
00:15:19.280
about what hormones actually do to create this thing
link |
00:15:23.260
that we call masculinization or feminization.
link |
00:15:26.240
So let's start with development.
link |
00:15:29.200
Sperm meets egg.
link |
00:15:30.480
Everything that happens before that
link |
00:15:31.700
is a topic of the next episode.
link |
00:15:34.080
But sperm meets egg, this is mammalian reproduction.
link |
00:15:37.400
And that egg starts to duplicate.
link |
00:15:39.040
It starts to make more of itself.
link |
00:15:40.740
It makes more cells.
link |
00:15:41.840
And eventually some of those cells become skin.
link |
00:15:43.660
Some of those cells become brain.
link |
00:15:45.200
Some of those cells become muscle.
link |
00:15:46.620
Some of those cells become fingers.
link |
00:15:48.560
All the stuff that makes up the brain and body plan.
link |
00:15:53.400
In addition, there are hormones that come both
link |
00:15:57.000
from the mother and from the developing baby,
link |
00:16:01.080
the developing fetus that impact
link |
00:16:03.480
whether or not the brain will be
link |
00:16:05.120
what they call organized masculine or organized feminine.
link |
00:16:08.780
And as I say this,
link |
00:16:10.480
I want you to try and discard
link |
00:16:12.160
with the cultural connotations
link |
00:16:13.920
or your psychological connotations
link |
00:16:15.720
of what masculinization and feminization are
link |
00:16:18.760
because we're only centering on the biology.
link |
00:16:22.120
So typically people have either two X chromosomes
link |
00:16:28.480
and the traditional language around that
link |
00:16:30.200
is that person is female, right?
link |
00:16:33.000
Or an X chromosome and a Y chromosome
link |
00:16:35.620
and that person will become male.
link |
00:16:37.880
Now it's not always the case.
link |
00:16:39.600
There are cases where it's XXY
link |
00:16:42.320
where there are two X chromosomes plus a Y chromosome.
link |
00:16:45.040
There are also cases where it's XYY
link |
00:16:47.580
where there are two Y chromosomes
link |
00:16:49.240
and these have important biological
link |
00:16:51.520
and psychological impacts.
link |
00:16:54.520
So the first thing we need to establish
link |
00:16:56.080
is that there is something called chromosomal sex.
link |
00:16:59.140
Whether or not there are two X chromosomes
link |
00:17:00.800
or an X and Y chromosome is what we call chromosomal sex.
link |
00:17:05.800
But the next stage of separating out the sexes
link |
00:17:10.120
is what we call gonadal sex.
link |
00:17:12.240
Typically, not always,
link |
00:17:14.000
but typically if somebody has testes for their gonads
link |
00:17:18.640
we think of them as male.
link |
00:17:21.040
And if somebody has ovaries, we think of them as female.
link |
00:17:24.940
Although that's not always the case either
link |
00:17:27.300
but let's just explore the transition
link |
00:17:29.960
from chromosomal sex to gonadal sex
link |
00:17:32.000
because it's a fascinating one
link |
00:17:33.800
that we all went through in some form or another.
link |
00:17:37.120
So this XY that we typically think of
link |
00:17:40.800
as promoting masculinization of the fetus.
link |
00:17:45.120
We say that because on the Y chromosome, there are genes
link |
00:17:50.400
and those genes have particular functions
link |
00:17:52.860
that suppress female reproductive organs.
link |
00:17:57.240
So on the Y chromosome, there's a gene
link |
00:18:00.400
which encodes for something called
link |
00:18:02.380
a Mullerian inhibiting hormone.
link |
00:18:04.660
So there's actually a hormone
link |
00:18:06.920
that's programmed by the Y chromosome
link |
00:18:09.180
that inhibits the formation of Mullerian ducts
link |
00:18:12.040
which are an important part
link |
00:18:13.200
of the female reproductive apparatus.
link |
00:18:16.760
That's critical because already we're seeing the transition
link |
00:18:19.680
between chromosome Y chromosome and gonad.
link |
00:18:23.140
And other genes on the Y chromosome
link |
00:18:26.180
promote the formation of testes.
link |
00:18:28.400
So there are genes like the SRY gene
link |
00:18:30.440
and other genes that promote the formation of testes
link |
00:18:33.000
while they also inhibit the formation of the Mullerian ducts.
link |
00:18:37.360
So the transition from chromosomal sex to gonadal sex
link |
00:18:40.960
is a very important distinction.
link |
00:18:43.320
It's kind of a fork in the road
link |
00:18:44.920
that happens very early in development
link |
00:18:46.800
while fetuses are still in the embryo.
link |
00:18:49.480
Now, what's interesting as well
link |
00:18:52.560
is that just because there's a Y chromosome
link |
00:18:55.440
that can suppress Mullerian duct formation
link |
00:18:57.480
and there are other genes on the Y chromosome
link |
00:18:59.480
that promote teste development,
link |
00:19:02.080
the placenta itself is an endocrine organ.
link |
00:19:05.360
I think most people don't know this
link |
00:19:06.480
but the placenta is an endocrine organ.
link |
00:19:08.760
As well, the mother, which of course is carrying the fetus,
link |
00:19:12.200
has an adrenal gland which can produce testosterone.
link |
00:19:16.640
There are instances, for example,
link |
00:19:19.160
where a mother has either a tumor
link |
00:19:21.400
or for some other reason is secreting large levels
link |
00:19:24.320
of testosterone while carrying a fetus that is XX
link |
00:19:28.600
and that leads to what we would call masculinization
link |
00:19:31.640
of certain aspects of the fetus.
link |
00:19:33.040
Typically, that would be enlarged clitoris.
link |
00:19:35.780
There are also some examples of other phenotypes on the body
link |
00:19:39.120
that are created even though
link |
00:19:40.560
it's a purely XX chromosomal baby.
link |
00:19:44.080
So we have to distinguish
link |
00:19:45.840
between chromosomal sex, gonadal sex,
link |
00:19:48.480
and then there's what we call hormonal sex
link |
00:19:51.520
which is the effects of the steroid hormones,
link |
00:19:55.160
estrogen and testosterone and their derivatives
link |
00:19:57.960
on what we call morphological sex
link |
00:20:00.800
or the shape of the baby and the human and the genitalia
link |
00:20:03.620
and the jaw and all these other things.
link |
00:20:05.480
And so it actually is quite complicated.
link |
00:20:07.780
So it's a long distance from chromosomes to gender identity
link |
00:20:11.980
and gender identity has a lot of social influences and roles.
link |
00:20:15.560
This is an area that right now is very dynamic
link |
00:20:17.760
and in the discussion out there, as you know,
link |
00:20:19.960
but just getting from chromosomal sex
link |
00:20:21.980
to what we would call gonadal sex
link |
00:20:24.920
and hormonal sex and morphological sex
link |
00:20:27.480
involves a number of steps.
link |
00:20:28.760
So today we're going to talk about those steps
link |
00:20:31.020
and there's some fascinating things
link |
00:20:32.800
that do indeed relate to tools,
link |
00:20:35.480
do indeed relate to some important behavioral choices,
link |
00:20:39.400
important choices about things to avoid while pregnant.
link |
00:20:43.160
And for those of you that are not pregnant,
link |
00:20:44.940
things to avoid if you're thinking
link |
00:20:46.500
about eventually having children
link |
00:20:48.540
and that is not to drive development
link |
00:20:50.480
in one direction or another,
link |
00:20:51.760
but there are examples where there are some deleterious
link |
00:20:54.600
things in our environment
link |
00:20:55.880
that can actually negatively impact
link |
00:20:58.160
what we call sexual development overall,
link |
00:21:00.320
regardless of chromosomal background.
link |
00:21:02.440
So let's get started with that.
link |
00:21:04.120
Let's talk a little bit more about what hormones do.
link |
00:21:07.200
Hormones generally have two categories of effects.
link |
00:21:09.800
They can either be very fast or they can be very slow.
link |
00:21:12.500
There are hormones like cortisol and adrenaline,
link |
00:21:15.240
which act very fast.
link |
00:21:16.800
Adrenaline can increase your heart rate very fast
link |
00:21:20.280
when it's secreted into the body.
link |
00:21:21.480
Cortisol can be a little bit slower,
link |
00:21:23.180
but it also can have some very fast effects.
link |
00:21:25.120
And then there are hormones like testosterone and estrogen,
link |
00:21:29.120
which we refer to as the sex steroid hormones.
link |
00:21:33.140
The sex steroid hormones can have quick effects
link |
00:21:36.600
through signaling, meaning they can attach to cells
link |
00:21:38.980
and make those cells do different things.
link |
00:21:40.960
They can have actually quite quick effects on the brain.
link |
00:21:43.440
A lot of people don't know this,
link |
00:21:44.800
but there are some very fast effects
link |
00:21:46.580
of estrogen and testosterone, as well as long-term effects.
link |
00:21:50.360
These molecules, for those of you that are interested,
link |
00:21:53.200
are what are called lipophilic,
link |
00:21:54.520
which just means that they like fatty stuff.
link |
00:21:56.240
They can actually pass through fatty membranes.
link |
00:21:58.160
And because the outside of cells,
link |
00:22:00.480
as well as what's called the nuclear envelope,
link |
00:22:02.560
where all the DNA contents and stuff are stuffed inside,
link |
00:22:05.720
are made of lipid, of fat,
link |
00:22:09.240
these steroid hormones can actually travel into cells
link |
00:22:12.120
and then get into the,
link |
00:22:14.720
basically interact with the DNA of cells
link |
00:22:16.880
in order to control gene expression.
link |
00:22:18.560
So they can change the sorts of things
link |
00:22:21.160
that cells will become,
link |
00:22:22.480
and they can change the way that cells function
link |
00:22:24.400
in a long-term way.
link |
00:22:25.600
And that's actually how the presence of these genes,
link |
00:22:28.860
like SRY and molarion-inhibiting hormone,
link |
00:22:31.640
lead to reductions or elimination, I should say,
link |
00:22:35.800
of things like the molarion ducts
link |
00:22:37.440
and promote instead what's called in males,
link |
00:22:39.400
the Wolfian ducts,
link |
00:22:41.180
or promote the development of testes rather than ovaries.
link |
00:22:44.520
So all you need to know is that hormones have short-term
link |
00:22:47.600
and long-term effects,
link |
00:22:48.600
and the long-term effects are actually related
link |
00:22:51.000
to their effects on genes
link |
00:22:52.840
and how those genes are expressed or repressed
link |
00:22:56.200
in order to prevent them
link |
00:22:57.380
from having particular proteins made.
link |
00:23:00.280
So these hormones, these steroid hormones,
link |
00:23:03.040
are exceedingly powerful.
link |
00:23:05.280
And if we're going to have a discussion
link |
00:23:07.160
about masculinization or feminization, et cetera,
link |
00:23:09.980
you also need to think about the counterpart.
link |
00:23:11.520
It's not just about masculinizing the body
link |
00:23:13.480
or feminizing the body and brain,
link |
00:23:15.020
it's also about demasculinizing the brain in many cases
link |
00:23:19.280
as a normal biological function
link |
00:23:21.680
of typically of XX females,
link |
00:23:25.000
and defeminization, the suppression of certain pathways
link |
00:23:27.960
that are related to feminization of the body and brain.
link |
00:23:31.340
But there are some really fascinating twists in this story.
link |
00:23:35.520
So I've just thrown a lot of biology at you,
link |
00:23:37.980
but this is where it all starts to get incredibly surprising.
link |
00:23:43.620
You would think that it's straightforward, right?
link |
00:23:47.160
You have a Y chromosome,
link |
00:23:49.280
you suppress the female reproductive pathway
link |
00:23:53.400
like the malaria ducts,
link |
00:23:55.660
you promote the development of testes,
link |
00:23:58.400
and then testes make testosterone,
link |
00:24:00.580
and then it organizes the brain male,
link |
00:24:02.700
and it wants to do male-like things,
link |
00:24:04.200
and then in females, you get estrogen,
link |
00:24:06.720
and it wants to do female-like things,
link |
00:24:08.800
and air quotes here for all of this.
link |
00:24:11.120
And it turns out that isn't how it works at all.
link |
00:24:15.460
Here's where it's interesting.
link |
00:24:16.480
We have to understand that there are effects
link |
00:24:19.020
of these hormones, testosterone and estrogen,
link |
00:24:22.640
on what are called primary sexual characteristics,
link |
00:24:25.700
which are the ones that you're born with,
link |
00:24:28.500
secondary sexual characteristics,
link |
00:24:30.520
which are the ones that show up in puberty,
link |
00:24:32.240
and these are happening in the brain,
link |
00:24:34.040
and body, and spinal cord.
link |
00:24:35.880
And so I'm going to disentangle all this for you
link |
00:24:37.500
by giving you some examples.
link |
00:24:39.760
First, let's talk about the development
link |
00:24:41.260
of primary sexual characteristics,
link |
00:24:43.120
the ones that show up at birth.
link |
00:24:46.320
And one of the more dramatic examples of this
link |
00:24:49.680
comes from the role of testosterone
link |
00:24:53.160
in creating the external genitalia.
link |
00:24:56.280
Now, you might think it's just straightforward.
link |
00:24:58.400
If there's testes, because there's a Y chromosome,
link |
00:25:01.240
you've got a gene that codes for the development of testes,
link |
00:25:05.360
you get testosterone, and the penis grows,
link |
00:25:08.120
and the baby is born with a penis.
link |
00:25:09.600
One of the first things that happens
link |
00:25:10.540
when the baby comes out is they look at the genitalia,
link |
00:25:12.960
and they try and make an assessment
link |
00:25:14.320
on whether or not it's a, quote, boy,
link |
00:25:16.000
or it's a, quote, girl, right?
link |
00:25:18.060
That's been done for a very long time
link |
00:25:20.520
throughout human history.
link |
00:25:24.360
It turns out that it's not testosterone
link |
00:25:27.240
that's responsible for the development of the penis
link |
00:25:30.600
in a baby that has an X chromosome and a Y chromosome.
link |
00:25:35.560
It's a different androgen.
link |
00:25:37.600
Androgen is just a category of hormones
link |
00:25:40.720
that includes testosterone,
link |
00:25:42.960
but testosterone is converted in the fetus
link |
00:25:47.380
to something called dihydrotestosterone,
link |
00:25:50.000
and that's accomplished through an enzyme
link |
00:25:52.240
called 5-alpha reductase.
link |
00:25:53.920
Now, dihydrotestosterone has important effects
link |
00:25:56.880
later in life too.
link |
00:25:58.220
We will talk about those.
link |
00:25:59.160
In fact, if you just want to know,
link |
00:26:00.840
dihydrotestosterone is what we would call
link |
00:26:03.120
the dominant androgen in males.
link |
00:26:05.600
It's responsible for aggression.
link |
00:26:07.120
It's responsible for a lot of muscular strength.
link |
00:26:10.980
It's involved in beard growth and male pattern baldness.
link |
00:26:14.440
We're going to talk about all of that.
link |
00:26:15.840
But dihydrotestosterone has powerful effects
link |
00:26:19.360
in determining the genitalia
link |
00:26:21.340
while the baby is still in the embryo.
link |
00:26:23.480
So this ends, there's testosterone that's made,
link |
00:26:27.780
and that testosterone gets converted
link |
00:26:30.100
by this enzyme, 5-alpha reductase,
link |
00:26:32.620
in a little structure called the tubercle.
link |
00:26:34.940
That tubercle will eventually become the penis.
link |
00:26:37.920
So you say, okay, straightforward.
link |
00:26:39.660
This testosterone's converted to dihydrotestosterone,
link |
00:26:42.700
and then if there's dihydrotestosterone,
link |
00:26:44.960
it controls penis growth.
link |
00:26:46.600
And indeed, that's the case.
link |
00:26:48.600
So that's a primary sexual characteristic.
link |
00:26:51.120
That baby will then grow up, and later, during puberty,
link |
00:26:56.400
there will be the release of a molecule,
link |
00:26:58.040
I talked about this last episode,
link |
00:26:59.420
called kispeptin, K-I-S-S-P-E-P-T-I-N, kispeptin,
link |
00:27:04.160
which will cause the release of some other hormones,
link |
00:27:06.120
canadotropin-releasing hormone, luteinizing hormone,
link |
00:27:08.040
will stimulate the testes to make testosterone.
link |
00:27:10.080
So in puberty, testosterone leads to further growth
link |
00:27:13.720
and development of the penis,
link |
00:27:15.200
as well as the accumulation or growth of pubic hair,
link |
00:27:19.940
deepening of the voice,
link |
00:27:20.920
all the secondary sexual characteristics, okay?
link |
00:27:24.280
So dihydrotestosterone creates what we would call
link |
00:27:28.400
the typical masculine phenotype
link |
00:27:30.780
for primary sexual characteristics,
link |
00:27:33.960
and produces, testosterone, excuse me,
link |
00:27:37.240
produces secondary sexual characteristics during puberty.
link |
00:27:41.700
There's a very interesting phenomenon
link |
00:27:43.660
that was published in the journal Science in the 1970s,
link |
00:27:46.800
for which now there's a wealth of scientific data.
link |
00:27:50.160
And this relates to a genetic mutation
link |
00:27:53.040
where 5-alpha reductase,
link |
00:27:55.320
the enzyme that converts testosterone
link |
00:27:57.740
to dihydrotestosterone, doesn't exist.
link |
00:28:00.580
It's mutated in a way in a genome that it doesn't exist.
link |
00:28:04.160
And this actually was first identified
link |
00:28:06.400
in the Dominican Republic.
link |
00:28:07.920
It has shown up elsewhere.
link |
00:28:10.000
It's quite rare, but where it shows up, it's robust.
link |
00:28:14.480
What happens is baby is born.
link |
00:28:17.300
Typically, when a baby is born,
link |
00:28:19.080
they don't measure chromosomes.
link |
00:28:20.600
They don't look at chromosomal sex, XX or XY.
link |
00:28:22.960
That's not typically done nowadays.
link |
00:28:25.240
Baby is born.
link |
00:28:26.460
If you were to look at that baby, it would look female.
link |
00:28:30.080
There would be very little or no external penis.
link |
00:28:34.300
And so people would say, it's a girl,
link |
00:28:35.760
and they might have the celebration, it's a girl.
link |
00:28:38.160
And I guess now they call them gender reveal parties
link |
00:28:40.760
or something like that.
link |
00:28:41.600
I don't know about this.
link |
00:28:42.420
But anyway, the baby would reveal its external genitalia
link |
00:28:49.680
simply by being there and being naked when it's born.
link |
00:28:52.200
Has nothing to do with gender.
link |
00:28:53.600
It has to do with genitalia and sex.
link |
00:28:56.800
That baby would be born.
link |
00:28:58.580
And what was observed is that from time to time,
link |
00:29:02.920
that baby, after being raised as a girl,
link |
00:29:06.020
perfectly happy as a girl,
link |
00:29:08.100
would, around the age of 11 or 12 or 13,
link |
00:29:12.800
would suddenly start to sprout a penis.
link |
00:29:15.520
There's actually a name for this.
link |
00:29:16.680
It's called huevidosis,
link |
00:29:18.280
which the translation is more or less penis at 12.
link |
00:29:23.040
And as strange as this might sound,
link |
00:29:25.640
it makes sense if you understand the underlying mutation.
link |
00:29:28.520
What happens in these children, these huevidosis,
link |
00:29:32.640
is that the child is born.
link |
00:29:35.480
It has testes, which are not descended, so up in the body.
link |
00:29:40.080
They're not making a lot of testosterone early on.
link |
00:29:44.120
They weren't able to convert testosterone
link |
00:29:46.520
to dihydrotestosterone
link |
00:29:47.720
because they lack this enzyme, 5-alpha reductase.
link |
00:29:51.360
As a consequence, the primary sexual characteristic
link |
00:29:54.440
of external male genitalia, penis, doesn't develop.
link |
00:29:59.480
And then what happens is the baby grows up
link |
00:30:02.440
as a young child, essentially as treated as a girl.
link |
00:30:05.760
Generally, they report being pretty comfortable as girls,
link |
00:30:08.860
although not always.
link |
00:30:10.320
And then testosterone starts getting secreted
link |
00:30:13.700
from the testes because kispeptin in the brain
link |
00:30:16.440
signals through gonadotropin and luteinizing hormone,
link |
00:30:18.760
travels down to the testes.
link |
00:30:20.000
The testes start churning out testosterone
link |
00:30:22.120
and there's a secondary growth of the penis.
link |
00:30:24.560
And all of a sudden there's a penis.
link |
00:30:25.800
And this leads to some very complicated situations
link |
00:30:28.640
in families and culturally.
link |
00:30:30.660
And actually the outcomes in terms of whether or not
link |
00:30:33.960
these children decide to self-identify as males or females
link |
00:30:37.680
and how people treat them actually varies quite a lot.
link |
00:30:40.540
There's actually been a kind of an adopting
link |
00:30:43.220
of a third category of sex and gender in the suavodosis
link |
00:30:48.080
in order to just offer them the opportunity
link |
00:30:51.040
to explore not just what would be a typical kind of girl
link |
00:30:55.880
or woman or boy or man phenotype, but something in between,
link |
00:30:59.480
something that some people call intersex,
link |
00:31:01.160
although intersex and pseudohermaphroditism
link |
00:31:03.680
is actually a separate thing altogether.
link |
00:31:05.820
So it's fascinating.
link |
00:31:06.660
And the point here is that dihydrotestosterone,
link |
00:31:11.720
not testosterone is responsible for this primary growth
link |
00:31:15.520
of the penis and that testosterone later is involved
link |
00:31:19.100
in the secondary sexual characteristics,
link |
00:31:21.420
deepening in the voice, et cetera.
link |
00:31:23.920
Now, this is where the information gets even more
link |
00:31:25.960
interesting and applies to essentially everybody.
link |
00:31:30.920
You might think that testosterone,
link |
00:31:34.040
because it masculinizes the body
link |
00:31:37.400
in the secondary sexual characteristic way
link |
00:31:41.200
and because dihydrotestosterone, another androgen,
link |
00:31:45.300
masculinizes the primary sexual characteristics,
link |
00:31:48.800
the growth of the penis early on,
link |
00:31:50.400
that testosterone must masculinize the brain.
link |
00:31:53.880
And there are in fact aspects of masculinization
link |
00:31:58.360
of the brain and body that are independent of genitalia.
link |
00:32:02.700
Now it might be obvious to some of you,
link |
00:32:03.940
but some people probably don't realize that.
link |
00:32:05.880
Yes, indeed, the brain has receptors for testosterone.
link |
00:32:11.840
It also has receptors for estrogen.
link |
00:32:15.420
But the fascinating thing is that if you look at the brains
link |
00:32:20.260
of people that have Y chromosomes
link |
00:32:22.880
and that have testes and that make testosterone,
link |
00:32:25.180
and you look at the brains of people
link |
00:32:27.080
that don't have Y chromosomes or testes
link |
00:32:29.760
and therefore make far less testosterone in general,
link |
00:32:36.000
what you realize is that the cells in the brain
link |
00:32:39.100
that differ between what I'll call males and females,
link |
00:32:42.020
but between XY and XX have receptors for testosterone,
link |
00:32:48.880
but the masculinization of the brain
link |
00:32:51.440
is not accomplished by testosterone.
link |
00:32:54.720
I want to repeat this.
link |
00:32:55.560
The masculinization of the brain
link |
00:32:57.360
is not accomplished by testosterone.
link |
00:32:59.760
It is accomplished by estrogen.
link |
00:33:04.080
Testosterone can be converted into estrogen
link |
00:33:06.960
by an enzyme called aromatase.
link |
00:33:09.680
This is vitally important to understand.
link |
00:33:11.440
Testosterone can be converted into estrogen
link |
00:33:13.560
by something called aromatase.
link |
00:33:15.520
I'll give an example of where this happens later in life
link |
00:33:19.040
to just illustrate the principle
link |
00:33:20.540
and really embedded in your mind.
link |
00:33:23.640
During puberty in boys, XY chromosome individuals,
link |
00:33:28.840
it's not uncommon for there to be transient
link |
00:33:31.400
or sometimes long lasting breast bud development.
link |
00:33:34.560
Testosterone goes up during puberty
link |
00:33:36.840
for the reasons we talked about before,
link |
00:33:39.240
and some of that testosterone gets converted into estrogen
link |
00:33:43.060
by an enzyme called aromatase.
link |
00:33:46.000
Aromatase is made by several sources in the body.
link |
00:33:49.280
One of the main sources is body fat.
link |
00:33:51.880
So it can make a lot of aromatase.
link |
00:33:53.640
Sometimes you'll even see a fairly dramatic
link |
00:33:56.440
breast development in males during puberty.
link |
00:33:58.520
Sometimes it's transient, sometimes it's not.
link |
00:34:00.600
The other place where you see this
link |
00:34:02.080
is in athletes and bodybuilders
link |
00:34:04.840
that take a lot of anabolic steroids
link |
00:34:06.920
that take high levels of androgens.
link |
00:34:09.240
So they'll be taking testosterone
link |
00:34:11.040
at super physiological doses.
link |
00:34:13.640
Sometimes not always,
link |
00:34:15.000
they will convert some of that testosterone into estrogen
link |
00:34:17.820
and they'll get what's called gynecomastia,
link |
00:34:20.080
which is the development of male breast tissue.
link |
00:34:23.120
Sometimes they'll get it cut out surgically.
link |
00:34:25.480
Other times they'll start trying to take estrogen blockers
link |
00:34:27.800
in order to try and suppress it,
link |
00:34:29.440
or they'll try and block prolactin.
link |
00:34:31.140
It's a topic that we're going to get into in more detail,
link |
00:34:33.560
but what's important here is to understand
link |
00:34:35.480
that testosterone can be converted
link |
00:34:36.840
into the estrogen by aromatase.
link |
00:34:39.080
Aromatase is not just made in body fat.
link |
00:34:41.560
There are neurons in the brain that make aromatase
link |
00:34:44.880
and convert testosterone into estrogen,
link |
00:34:47.280
and it is testosterone converted into estrogen.
link |
00:34:52.360
In other words, it's estrogen
link |
00:34:53.760
that masculinizes the XY individual,
link |
00:34:58.060
that masculinizes the brain.
link |
00:35:00.080
And this has profound effects on all sorts of things,
link |
00:35:03.560
on behavior, on outlook in the world, et cetera.
link |
00:35:07.800
But I think most people don't realize
link |
00:35:09.180
that it's estrogen that comes from testosterone
link |
00:35:12.080
that masculinizes the male brain, the XY brain,
link |
00:35:15.400
not testosterone nor dihydrotestosterone.
link |
00:35:19.260
So I just want to mention some tools.
link |
00:35:21.340
You might be asking yourself,
link |
00:35:22.640
how could tools possibly come up
link |
00:35:24.520
at this stage of the conversation
link |
00:35:26.000
where we're talking about sexual development
link |
00:35:28.240
and we're talking about the differentiation
link |
00:35:30.440
of tissues in the body?
link |
00:35:32.560
Well, this is true both for children and parents and adults.
link |
00:35:35.880
I want to emphasize that there are things
link |
00:35:39.800
that are environmental and there are things that people use
link |
00:35:44.100
that in their homes sometimes
link |
00:35:46.040
that actually can impact hormone levels
link |
00:35:49.040
and can impact sexual development in fairly profound ways.
link |
00:35:52.800
And I want to be very clear.
link |
00:35:54.640
This is not me pulling from some rare journal
link |
00:35:58.520
I've never heard of it.
link |
00:35:59.640
This is pulling from textbooks.
link |
00:36:01.880
In particular, today, I'm guiding a lot of the conversation
link |
00:36:04.400
on work on behavioral endocrinology.
link |
00:36:08.540
This is a book by Randy Nelson and Lance Crigfield,
link |
00:36:12.240
true experts in the field.
link |
00:36:14.060
I'm going to talk about some of the work from Tyrone Hayes
link |
00:36:16.520
from UC Berkeley about environmental toxins
link |
00:36:20.000
and their impacts on some of these things
link |
00:36:21.760
like testosterone and estrogen.
link |
00:36:23.820
I'm going to touch into them.
link |
00:36:25.320
I'm going to give some anecdotal evidence
link |
00:36:27.320
that's grounded in studies,
link |
00:36:28.720
which we will provide in the caption
link |
00:36:30.580
or that I'll reference here.
link |
00:36:32.320
One of those that's actually really interesting
link |
00:36:34.760
but helps illustrate the principle
link |
00:36:36.740
that we've been talking about is a few years ago,
link |
00:36:39.120
there was a lot of excitement about evening primrose oil.
link |
00:36:41.960
Evening primrose oil is in a lot of products
link |
00:36:45.460
that typically are associated with skin beauty
link |
00:36:47.720
and skin health.
link |
00:36:48.720
And so I'm generalizing here,
link |
00:36:51.040
but typically it was mothers or sisters that were using it.
link |
00:36:55.360
And there were actually examples starting to crop up
link |
00:36:58.160
of young boys getting accelerated breast bud development
link |
00:37:02.460
from skin contact with women
link |
00:37:06.400
who were using evening primrose oil.
link |
00:37:08.320
So evening primrose oil is chemically a lot like estrogen
link |
00:37:12.600
and it has a lot of estrogenic compounds.
link |
00:37:14.840
There are a number of things out there like this.
link |
00:37:17.560
So believe it or not, things like pine pollen
link |
00:37:19.840
look very much like testosterone.
link |
00:37:21.660
Structurally, they are more or less are testosterone.
link |
00:37:24.760
Their bioavailability in humans isn't as clear.
link |
00:37:27.540
Evening primrose oil has a lot of estrogenic elements to it,
link |
00:37:31.900
just structurally how it's built.
link |
00:37:33.560
And so there were cases where boys were understandably
link |
00:37:37.280
being hugged by their mom or maybe even like showering
link |
00:37:39.720
and taking a, using the evening primrose oil solution.
link |
00:37:43.760
Those things will actually change levels of estrogens
link |
00:37:47.400
in boys and girls.
link |
00:37:48.880
And so this wasn't just an issue for young boys.
link |
00:37:50.880
This was also an issue for young girls.
link |
00:37:52.320
So it's not that evening primrose oil is bad.
link |
00:37:55.700
It's just that many of you have probably heard
link |
00:37:58.060
about the dangers of soy and isoflavones
link |
00:38:00.560
and things like that.
link |
00:38:01.740
The impact of soy on estrogen levels
link |
00:38:04.040
is there are some decent evidence to support that.
link |
00:38:07.400
However, there's a lot of other factors
link |
00:38:09.600
that are more severe.
link |
00:38:10.480
And one of those is this evening primrose oil.
link |
00:38:13.120
So regardless of age, let's just put it this way
link |
00:38:16.400
because people might be wanting to drive their hormones
link |
00:38:18.960
more estrogenic or more androgenic.
link |
00:38:22.560
How could I know what your preference is?
link |
00:38:24.360
I don't know.
link |
00:38:25.240
But in any case, things like evening primrose oil
link |
00:38:29.360
can actually promote estrogenic pathways in the body
link |
00:38:32.480
and some of it can go transdermal.
link |
00:38:34.160
Likewise, because testosterone replacement therapy
link |
00:38:37.680
is fairly widespread nowadays
link |
00:38:39.520
and some people accomplish that through cream,
link |
00:38:41.480
it's pretty well understood that if someone's taking that,
link |
00:38:44.760
that they want to avoid contact with anyone,
link |
00:38:48.060
skin contact with anyone that is trying to promote
link |
00:38:52.600
more estrogenic activity in their body
link |
00:38:56.360
and especially in children.
link |
00:38:57.640
So that's one.
link |
00:38:58.520
The other is this issue of environmental factors.
link |
00:39:02.240
Now this, again, I'm just going to highlight
link |
00:39:05.040
when one starts talking about environmental factors
link |
00:39:07.720
and how they're poisoning us or disrupting growth
link |
00:39:10.240
or fertility rates,
link |
00:39:11.600
it can start to sound a little bit crazy
link |
00:39:13.880
except when you start to actually look
link |
00:39:15.560
at some of the real data,
link |
00:39:17.080
data from quality research labs
link |
00:39:19.120
funded by federal government,
link |
00:39:21.060
funded not from companies or other sources
link |
00:39:23.780
that are really aimed at understanding
link |
00:39:25.120
what the underlying biology is.
link |
00:39:26.760
And for that, we should all be grateful
link |
00:39:30.600
to Tyrone Hayes at UC Berkeley.
link |
00:39:33.280
I remember way back when I was a graduate student
link |
00:39:35.800
in the late 90s, goodness, at UC Berkeley.
link |
00:39:39.780
And I remember him, he was studying frogs.
link |
00:39:41.980
He was talking about developmental defects
link |
00:39:45.040
in these frogs that live in different waters around,
link |
00:39:47.920
it was California, but also elsewhere.
link |
00:39:50.600
And he identified a substance which is present
link |
00:39:53.260
in a lot of waterways throughout this country
link |
00:39:55.540
and other countries, so US and beyond,
link |
00:39:58.360
certainly not just restricted to California,
link |
00:40:00.400
which is atrazine, this is A-T-R-A-Z-I-N-E.
link |
00:40:04.840
Again, this is the stuff of textbooks
link |
00:40:06.520
and it causes severe testicular malformations.
link |
00:40:10.260
So again, atrazine exposure is serious.
link |
00:40:13.400
And what's interesting is if you look at the data,
link |
00:40:17.640
what you find is that at sites in Western
link |
00:40:20.380
and Midwestern sections of the United States,
link |
00:40:22.480
10 to 92% of male frogs, these were frogs mind you,
link |
00:40:27.120
had testicular abnormalities.
link |
00:40:29.160
And the most severe testicular malformations
link |
00:40:32.280
were in the testes rather than in the sperm.
link |
00:40:35.040
So it's actually the organ itself, the gonad itself.
link |
00:40:37.940
Now, it's very well known now that atrazine
link |
00:40:42.680
is in many herbicides.
link |
00:40:44.360
And so, whereas I would say in the 80s and 90s,
link |
00:40:47.860
the discussion around herbicides and their negative effects
link |
00:40:51.320
was considered kind of like hippie dippie stuff
link |
00:40:53.300
or the stuff you hear about it,
link |
00:40:56.120
your local community markets
link |
00:40:57.720
and these kind of new age communities,
link |
00:40:59.520
now there's very solid data from federally funded labs
link |
00:41:04.360
at major universities that have been peer reviewed
link |
00:41:06.860
and published in excellent journals,
link |
00:41:09.000
showing that indeed many of these herbicides
link |
00:41:11.200
can have negative effects primarily by impacting
link |
00:41:15.460
the ratios of these hormones in either the mothers
link |
00:41:19.820
or in the testes, altering the testes of the fathers
link |
00:41:24.820
or direct effects on developing young animals
link |
00:41:29.260
and potentially humans.
link |
00:41:30.340
And so you ask, well, what about humans?
link |
00:41:32.140
Frogs are wonderful, but what about humans?
link |
00:41:35.140
So here are the data on what's happening.
link |
00:41:38.780
And this isn't all going to be scary stuff.
link |
00:41:41.380
We're also going to talk about tools to ameliorate
link |
00:41:43.700
and offset some of these effects.
link |
00:41:45.700
One would be be cautious with evening primrose
link |
00:41:47.700
as well as testosterone creams,
link |
00:41:49.220
depending on whether or not you want to be more androgenic
link |
00:41:51.740
or estrogenic, depending on your needs.
link |
00:41:54.940
But across human populations,
link |
00:41:57.080
sperm counts are indeed declining, okay?
link |
00:41:59.700
So in 1940, the average density of human sperm
link |
00:42:04.580
was 113 million per milliliter of semen.
link |
00:42:08.740
That's how it's measured.
link |
00:42:09.560
How many sperm per milliliter of semen?
link |
00:42:11.880
In 1990, this figure has dropped to 66.
link |
00:42:15.060
It went from 113 million per milliliter
link |
00:42:18.460
to 66 million per milliliter in the United States
link |
00:42:21.340
and Western Europe.
link |
00:42:22.640
So it's not just a US thing.
link |
00:42:24.140
Researchers also estimated that the volume of semen
link |
00:42:26.940
produced by men has dropped 20% in that time,
link |
00:42:29.680
reduced sperm count per ejaculation even further.
link |
00:42:32.660
So between 1981 and 1991,
link |
00:42:35.920
the ratio of normal spermatogenesis has decreased
link |
00:42:38.400
from 56.4% to 26.9%.
link |
00:42:43.620
So there's a lot that's happening,
link |
00:42:46.740
primarily because of these herbicides
link |
00:42:49.520
that are in widespread use to reduce sperm counts.
link |
00:42:52.340
And these are going to have profound effects,
link |
00:42:54.220
not just on sperm counts, but on development,
link |
00:42:57.180
sexual development at the level of the gonads and the brain,
link |
00:43:00.160
because you need testosterone to get you
link |
00:43:03.160
dihydrotestosterone for primary sexual characteristics.
link |
00:43:05.980
You need estrogen that's come from testosterone
link |
00:43:08.840
to masculinize the brain.
link |
00:43:09.980
And of course, we're not just focusing on sperm
link |
00:43:13.180
and testosterone.
link |
00:43:14.500
You of course also know that many of these herbicides
link |
00:43:18.180
are disrupting estrogens in a similar way,
link |
00:43:21.740
or are leading to hyper estrogenic states,
link |
00:43:26.500
which might explain why puberty is happening
link |
00:43:30.120
so much earlier in young girls these days.
link |
00:43:33.420
So there are a lot of things that are happening.
link |
00:43:35.220
Now, does this mean that you have to run around
link |
00:43:37.480
and neurotically avoid anything that includes
link |
00:43:41.180
things like atrazine,
link |
00:43:42.620
and should you be avoiding all kinds of herbicides?
link |
00:43:46.160
I don't know, that's up to you,
link |
00:43:47.820
but it does seem that these have pretty marked effects
link |
00:43:51.000
in both the animal studies and in the human studies.
link |
00:43:54.640
You can open up a textbook like the endocrinology textbook
link |
00:43:58.100
and find things like vinclozolin.
link |
00:44:00.460
This is V-I-N-C-L-O-Z-O-L-I-N,
link |
00:44:04.840
which is a fungicide and it's an anti-androgen.
link |
00:44:07.860
You give it to animals, to rats,
link |
00:44:09.680
and instead of forming a penis, they don't form a penis.
link |
00:44:12.140
They basically, it's not that they form a clitoris,
link |
00:44:16.180
they just don't form a penis.
link |
00:44:17.700
So let's talk about female sexual development.
link |
00:44:20.960
And as always,
link |
00:44:22.780
what we'll do is we'll talk about the normal biology.
link |
00:44:24.640
Then we'll talk a little bit about a kind of extraordinary
link |
00:44:28.900
or unusual set of cases,
link |
00:44:30.780
but we'll talk about them
link |
00:44:33.140
because they illustrate an important principle
link |
00:44:35.700
about how things work under typical circumstances.
link |
00:44:39.660
So there is a mutation
link |
00:44:44.180
called androgen insensitivity syndrome.
link |
00:44:46.920
And understanding how androgen insensitivity syndrome works
link |
00:44:50.980
can help you really understand
link |
00:44:52.700
how hormones impact sexual development.
link |
00:44:55.760
So here's how it works.
link |
00:44:57.460
There are individuals who are XY,
link |
00:45:00.060
so they have a Y chromosome,
link |
00:45:01.440
that are born, that make testosterone,
link |
00:45:06.260
they have testes, and they don't have molarion ducts
link |
00:45:10.180
because on the Y chromosome
link |
00:45:12.180
is this molarion inhibiting hormone.
link |
00:45:14.340
However, these individuals look completely female.
link |
00:45:18.560
And in general, they report feeling
link |
00:45:21.740
like girls when they're young, women when they're older.
link |
00:45:25.280
But there's something unusual that's happening
link |
00:45:27.900
in these individuals
link |
00:45:28.840
because they have an XY chromosomal type and not XX.
link |
00:45:34.260
So what's happening?
link |
00:45:35.540
Well, what's happening is
link |
00:45:37.620
the testes are making testosterone,
link |
00:45:39.940
but the receptor for testosterone is mutated.
link |
00:45:43.460
And therefore, the testes never descend.
link |
00:45:46.700
They don't have ovaries, they have testes,
link |
00:45:49.100
but the testes are internal.
link |
00:45:50.940
And so typically, these individuals find out
link |
00:45:53.920
that they are actually XY chromosomes
link |
00:45:55.900
so that their chromosomal sex is male, if you will,
link |
00:46:00.860
and their gonadal sex is male,
link |
00:46:03.580
but the gonads, the testes are inside the body,
link |
00:46:05.960
they don't actually develop a scrotum,
link |
00:46:07.940
they don't make ovaries,
link |
00:46:09.020
and when they don't menstruate around the time of puberty,
link |
00:46:12.180
that's a sign that something is different.
link |
00:46:15.180
And so they never menstruate around puberty,
link |
00:46:16.860
and if they look into this deeply enough,
link |
00:46:19.300
what you find is that they are actually XY,
link |
00:46:22.340
they make testosterone,
link |
00:46:23.360
but their body can't make use of the testosterone
link |
00:46:25.420
because they don't have the receptors.
link |
00:46:27.880
And the receptors are vitally important
link |
00:46:29.920
for most all of the secondary sexual characteristics
link |
00:46:34.140
that we talked about,
link |
00:46:35.020
body hair, penis growth during puberty, et cetera.
link |
00:46:38.880
They live fairly happy lives as females,
link |
00:46:42.100
although, of course, they can't conceive, right?
link |
00:46:44.060
They don't have a uterus, they don't have ovaries.
link |
00:46:47.260
They also, in general, don't produce sperm
link |
00:46:50.580
in quantities enough
link |
00:46:51.500
that they could actually reproduce with somebody else,
link |
00:46:54.020
although sometimes they can.
link |
00:46:55.580
And believe it or not, and I'm not going to name names,
link |
00:46:58.300
but there are actually reports of several people,
link |
00:47:02.380
fairly prominent people throughout history,
link |
00:47:04.540
who have had this androgen insensitivity syndrome,
link |
00:47:07.200
or people suspected they did.
link |
00:47:09.860
And the reason to not name names
link |
00:47:11.340
is that it gets right to the heart
link |
00:47:13.380
of whether or not they are male or female.
link |
00:47:16.180
How could you say, right?
link |
00:47:17.560
They have XY chromosomes,
link |
00:47:19.380
but gonadally, they have testes that are inside.
link |
00:47:22.420
And yet, if you looked at their bodies,
link |
00:47:24.740
if you looked at their faces,
link |
00:47:26.700
you would say, almost with certainty,
link |
00:47:29.660
that they appeared female.
link |
00:47:31.900
And that naturally occurring experiment
link |
00:47:36.100
points to the fact that testosterone
link |
00:47:38.700
that shows up in the body
link |
00:47:40.060
and impacts the things at the levels of the receptor
link |
00:47:42.800
has a profound effect on phenotype,
link |
00:47:44.740
on the external or body plan.
link |
00:47:47.940
So again, we're talking about this
link |
00:47:49.700
in order to illustrate the principle
link |
00:47:51.020
that in order to have its effects,
link |
00:47:53.180
a hormone doesn't just have to be present,
link |
00:47:55.560
that hormone actually has to be able to bind its receptor
link |
00:47:58.820
and take action on the target cells.
link |
00:48:01.920
And once again, I'll just throw out the example
link |
00:48:04.540
of where people are using performance-enhancing drugs,
link |
00:48:08.060
although that's a pretty broad statement.
link |
00:48:09.700
Nowadays, there's a lot of excitement
link |
00:48:11.100
about the so-called SARMs,
link |
00:48:12.780
which are more on the receptor side.
link |
00:48:16.140
And so we'll talk about this in a future episode.
link |
00:48:19.460
And I just say that as a teaser
link |
00:48:20.780
because the SARMs and what's happening right now
link |
00:48:23.020
in augmenting sports performance,
link |
00:48:25.160
both with testosterone directly,
link |
00:48:26.660
but also testosterone derivatives,
link |
00:48:28.120
and then also altering things at the level of the receptor
link |
00:48:31.300
is exceedingly interesting
link |
00:48:32.780
and is revealing to us the many ways
link |
00:48:36.300
in which hormones can impact brain and body in ways
link |
00:48:40.360
that we didn't suspect.
link |
00:48:41.540
Perhaps the simplest way to understand
link |
00:48:43.980
how estrogen and testosterone impact masculinization
link |
00:48:48.260
or feminization of the brain and behavior
link |
00:48:50.700
is from a statement.
link |
00:48:52.620
It's actually the closing sentence of an abstract
link |
00:48:55.020
that my colleague Narao Shah
link |
00:48:56.460
at Stanford School of Medicine published,
link |
00:48:59.960
which is that estrogen,
link |
00:49:02.500
again, it's estrogen that is aromatized from testosterone
link |
00:49:06.860
by aromatase, sets up the masculine repertoire of sexual
link |
00:49:12.160
and in animals and in humans, territorial behaviors.
link |
00:49:15.580
So it sets up the circuitry in the brain.
link |
00:49:17.900
Estrogen does that.
link |
00:49:19.400
Estrogen sets up the masculine circuitry in the brain.
link |
00:49:23.600
And testosterone is then what controls the display
link |
00:49:28.420
of those behaviors later in life.
link |
00:49:30.860
And I find that incredibly interesting.
link |
00:49:33.020
You would think it was just testosterone did one thing
link |
00:49:35.020
and estrogen did another,
link |
00:49:36.440
but it turns out that nature
link |
00:49:38.040
is far more interesting than that.
link |
00:49:40.340
Okay, so what are some things
link |
00:49:41.700
that impact sexual development early in life
link |
00:49:45.500
and later in life?
link |
00:49:47.980
Let's talk about cannabis.
link |
00:49:51.320
Let's talk about alcohol.
link |
00:49:53.580
And dare I say, let's talk about cell phones.
link |
00:49:56.700
Something that I never thought I would ever do
link |
00:49:59.400
either in this podcast or in the classroom,
link |
00:50:01.260
but these days there are really interesting data
link |
00:50:04.660
and I think you should be aware of them.
link |
00:50:06.340
First of all, cannabis, marijuana, THC.
link |
00:50:10.420
I realize that there are now
link |
00:50:12.900
a lot of different variants on this.
link |
00:50:15.720
There are a lot of different strains of cannabis.
link |
00:50:18.520
I personally am not a pot smoker.
link |
00:50:20.940
It's just not for me.
link |
00:50:23.060
I'm not talking about the moral or legal implications.
link |
00:50:25.780
In some states it's decriminalized,
link |
00:50:27.500
in other places it's really illegal,
link |
00:50:29.140
in other places it's basically legal.
link |
00:50:32.140
You have to check where you live and understand the laws.
link |
00:50:35.900
That's not what this is about.
link |
00:50:37.660
What we do know, however,
link |
00:50:39.760
is that with the exception of one study,
link |
00:50:43.620
there are many studies that point to the fact
link |
00:50:46.780
that THC and other things in cannabis
link |
00:50:51.060
promote significant increases in aromatase activity.
link |
00:50:57.140
Pot smokers aren't going to like this,
link |
00:50:58.660
especially male pot smokers aren't going to like this,
link |
00:51:00.840
but it's the reality.
link |
00:51:02.140
Remember, what you're hearing in the background
link |
00:51:04.980
is Costello snoring really loud.
link |
00:51:06.740
Should we put him on screen?
link |
00:51:08.140
He's not a cannabis smoker, but you can imagine why.
link |
00:51:10.820
Here, come here Costello, come here buddy, come here.
link |
00:51:13.340
He's asleep, come here.
link |
00:51:15.060
He's like, come here.
link |
00:51:16.100
There you go.
link |
00:51:20.220
This dog definitely does not need cannabis.
link |
00:51:23.820
This is his state for most of the time.
link |
00:51:25.420
He is highly, apparently he's asleep still.
link |
00:51:27.620
So some of you have asked to see Costello.
link |
00:51:30.140
If you're just listening on audio,
link |
00:51:31.460
maybe he'll give us something.
link |
00:51:33.220
That's a, oh, okay.
link |
00:51:34.380
We're going to let him get back to sleep.
link |
00:51:36.260
He's always here.
link |
00:51:37.180
Some of you have asked to see him.
link |
00:51:39.060
Costello is not a pot smoker either.
link |
00:51:42.460
He did have a dog sitter that was a pot smoker years ago.
link |
00:51:47.860
It was his favorite dog sitter, but I'm not a pot smoker.
link |
00:51:52.980
Again, no judgment, but here's the deal.
link |
00:51:55.980
That cannabis, and it's not clear if it's THC itself
link |
00:51:59.980
or other elements in the marijuana plant,
link |
00:52:02.740
promote aromatase activity.
link |
00:52:05.860
Now, this has been observed anecdotally
link |
00:52:09.500
where pot smokers have a higher incidence
link |
00:52:12.040
of developing something I mentioned before,
link |
00:52:13.900
gynecomastia, breast bud development,
link |
00:52:15.940
or full-blown breast development in males.
link |
00:52:19.520
There may be some women
link |
00:52:20.540
who want to increase their estrogenic activity.
link |
00:52:24.060
Remember, females make testosterone.
link |
00:52:27.060
It comes from the adrenals, right?
link |
00:52:28.960
They don't have testes, so it comes from the adrenals,
link |
00:52:31.900
and that testosterone can also be aromatized,
link |
00:52:34.420
although typically most of the aromatase activity
link |
00:52:37.520
that we're referring to in these examples is in males.
link |
00:52:39.800
So testosterone can increase estrogenic activity.
link |
00:52:42.940
So you might say, oh, therefore,
link |
00:52:44.780
does testosterone reduce sexual behavior?
link |
00:52:49.300
Does it create all sorts of things
link |
00:52:51.580
that are related to low testosterone?
link |
00:52:54.980
Not necessarily, not necessarily, and here's why.
link |
00:52:59.500
Estrogen itself in males and females
link |
00:53:03.620
is important for things like libido and sexual behavior.
link |
00:53:08.940
I'm going to repeat that.
link |
00:53:10.120
If estrogen is too low in males,
link |
00:53:12.120
it can actually inhibit libido and sexual behavior.
link |
00:53:15.820
So you don't want estrogen too high or too low,
link |
00:53:19.740
whether or not you're male or female.
link |
00:53:21.660
Now, of course, in females,
link |
00:53:23.520
estrogen levels tend to be higher than in males.
link |
00:53:26.900
I'm speaking very generally here.
link |
00:53:28.600
You just think back to the chromosomal sex.
link |
00:53:30.420
That's what I'm referring to when I say male or female,
link |
00:53:33.260
although there's nuance there, of course.
link |
00:53:35.540
In females, the testosterone that comes from the adrenals
link |
00:53:39.900
has a powerful effect on libido and desire to reproduce,
link |
00:53:44.660
and in the next episode,
link |
00:53:45.540
we're going to talk about how that works
link |
00:53:47.100
in its relationship to birth control,
link |
00:53:48.860
its relationship to menopause.
link |
00:53:50.500
We're also going to talk about how that whole thing works
link |
00:53:52.780
in males as well.
link |
00:53:54.440
But cannabis and other aspects of the marijuana plant
link |
00:53:59.400
can impact levels of testosterone and estrogen
link |
00:54:02.780
by increasing aromatase,
link |
00:54:04.220
and so people should be aware of that.
link |
00:54:06.780
As well, there are good data.
link |
00:54:08.540
I was able to find several studies on PubMed
link |
00:54:10.460
pointing to the fact that smoking marijuana
link |
00:54:13.180
during pregnancy can shift the pattern of hormones
link |
00:54:18.140
in the developing fetus,
link |
00:54:20.240
such that it promotes more estrogenic outcomes.
link |
00:54:24.020
Now, earlier I said that estrogen
link |
00:54:25.900
is what masculinizes the male brain.
link |
00:54:27.900
In utero, that's true,
link |
00:54:29.480
but the way that cannabis seems to work,
link |
00:54:31.420
at least from the studies I was able to identify,
link |
00:54:33.940
is that it promotes circulating estrogen in the body
link |
00:54:38.500
and therefore can counteract
link |
00:54:40.460
some of the masculinizing effects
link |
00:54:42.500
of things like testosterone and dihydrotestosterone
link |
00:54:46.900
on primary and secondary sexual characteristics.
link |
00:54:49.660
So I mention this because, you know,
link |
00:54:52.560
I think nowadays marijuana use is far more widespread
link |
00:54:55.980
and certainly during puberty,
link |
00:54:57.260
it can have profound effects on these hormonal systems.
link |
00:55:01.020
And so we'll do another episode
link |
00:55:03.020
that goes really deep into this,
link |
00:55:04.180
but yes, cannabis promotes estrogenic activity
link |
00:55:07.540
by increasing aromatase.
link |
00:55:09.840
Most everyone can appreciate that drinking during pregnancy
link |
00:55:13.260
is not good for the developing fetus.
link |
00:55:15.100
Fetal alcohol syndrome is a well-established
link |
00:55:18.440
negative outcome of pregnancy.
link |
00:55:21.240
And it's something that there are cognitive effects
link |
00:55:24.100
that are really bad.
link |
00:55:25.420
There's actually physical malformation, et cetera.
link |
00:55:29.020
So drinking during pregnancy, not good.
link |
00:55:31.700
Probably drinking during puberty, not good either
link |
00:55:33.900
because alcohol, in particular, certain things like beer,
link |
00:55:38.260
but other grain alcohols can increase estrogenic activity.
link |
00:55:43.260
Now, this isn't just about protecting young boys
link |
00:55:49.780
from estrogenic activity.
link |
00:55:51.480
It's also protecting girls from excessive
link |
00:55:56.000
or even hypoestrogenic effects of alcohol in puberty.
link |
00:56:02.000
Now, many teenagers drink, college students drink,
link |
00:56:05.900
and it's important to point out that puberty
link |
00:56:07.740
doesn't start on one day and end on another day.
link |
00:56:10.980
Puberty has a beginning, a middle, and an end.
link |
00:56:13.220
But development is really our entire lifespan.
link |
00:56:16.100
This idea that puberty has us open and close,
link |
00:56:20.100
that's just false.
link |
00:56:21.460
Okay, so we talked about cannabis.
link |
00:56:23.100
We talked about alcohol.
link |
00:56:24.860
Let's talk about cell phones.
link |
00:56:26.860
First of all, I use a cell phone.
link |
00:56:29.860
I use it very often,
link |
00:56:32.240
and I do not think they are evil devices.
link |
00:56:34.380
I think that they require some discipline
link |
00:56:37.920
in order to make sure that it does not become
link |
00:56:40.820
a negative force in one's life.
link |
00:56:42.220
So I personally restrict the number of hours
link |
00:56:44.220
that I'm on the phone and in particular on social media.
link |
00:56:47.020
I only answer email at particular times of day.
link |
00:56:49.860
But what about the cell phone itself?
link |
00:56:53.740
When I was a junior professor,
link |
00:56:56.380
I was a pre-tenure, early professor,
link |
00:56:58.980
I taught this class on neural circuits
link |
00:57:01.300
and health and disease.
link |
00:57:02.700
And one of the students asked me,
link |
00:57:04.860
are cell phones safe for the brain?
link |
00:57:07.140
And all the data pointed to the fact that they were,
link |
00:57:11.860
or at least there were no data showing that it wasn't.
link |
00:57:14.980
I still don't have the answer on that, frankly.
link |
00:57:16.780
I don't see a lot of studies about it.
link |
00:57:18.180
I'm not personally aware of any evidence
link |
00:57:20.460
in quality peer-reviewed studies
link |
00:57:22.220
showing that cell phones are bad for the brain
link |
00:57:24.520
or that holding the phone to the ear is bad
link |
00:57:26.520
or that Bluetooth is bad or any of that.
link |
00:57:28.360
I'm just not aware of any quality studies.
link |
00:57:30.340
If you are aware of quality studies, peer-reviewed studies,
link |
00:57:33.340
please reference them, put them in the comment section,
link |
00:57:36.580
send them to me, however you like.
link |
00:57:38.580
I'd love to see them.
link |
00:57:39.800
I'm not aware of them.
link |
00:57:40.640
However, I was very interested in a particular study
link |
00:57:45.680
that was published back in 2013 on rats.
link |
00:57:51.740
It was basically took a cell phone
link |
00:57:53.200
and put it under a cage of rats
link |
00:57:54.820
and looked at basically testicular
link |
00:57:57.180
and ovarian development in rats
link |
00:57:58.580
and saw minor but still statistically significant defects
link |
00:58:03.900
in ovarian and testicular development.
link |
00:58:06.640
Since then, and now returning to the literature,
link |
00:58:11.020
I've seen a absolute explosion of studies,
link |
00:58:16.060
some of which are in quality journals,
link |
00:58:18.260
some of which are in what I would call
link |
00:58:19.940
not blue ribbon journals,
link |
00:58:22.380
identifying defects in testicular and or ovarian development
link |
00:58:27.900
by mere exposure to cell phone emitted waves.
link |
00:58:33.160
Let's just call that.
link |
00:58:34.000
We don't know what they are.
link |
00:58:34.980
And this sounds almost crazy, right?
link |
00:58:37.520
Anytime somebody starts talking about EMFs
link |
00:58:39.420
and things like that, you kind of worry like,
link |
00:58:40.660
is this person okay?
link |
00:58:41.880
But look, the literature are pointing in a direction
link |
00:58:45.240
where chronic exposure of the gonads to cell phones
link |
00:58:50.580
could be creating serious issues
link |
00:58:52.420
in terms of the health at the cellular level
link |
00:58:55.500
and in terms of the output.
link |
00:58:56.900
So the output for the testes would be sperm production.
link |
00:59:00.900
Swimming speed in sperm is an important feature
link |
00:59:03.560
of sperm health. In the ovaries,
link |
00:59:05.380
it would be estrogenic output,
link |
00:59:07.620
how regular the cycles are.
link |
00:59:10.980
So in animals, the cycles are a little bit different
link |
00:59:13.120
than in humans. They don't have a menstrual cycle.
link |
00:59:15.140
They have an estrous cycle,
link |
00:59:16.580
which is generally around four days.
link |
00:59:20.040
I think that it's fair to say based on the literature
link |
00:59:23.420
that there are effects of cell phone emitted waves
link |
00:59:27.980
on gonadal development.
link |
00:59:29.580
The question is, what is the proximity of the cell phone
link |
00:59:33.000
to the gonads?
link |
00:59:33.840
Now I've taken the literature as I observe it.
link |
00:59:38.020
And then of course, we'll point you to in the captions.
link |
00:59:40.940
And I don't like to have my cell phone on and in my pocket.
link |
00:59:45.260
I'm well past puberty, but nonetheless,
link |
00:59:47.180
some of these effects were seen in adult animals.
link |
00:59:49.500
There are effects now that have been demonstrated in humans.
link |
00:59:52.500
So let's just talk about a couple of those effects.
link |
00:59:55.260
So a paper published in the journal Clinical Biochemistry
link |
00:59:58.620
from Eskander et al, looked at hormone profiles
link |
01:00:03.220
in people based on proximity to their phone
link |
01:00:08.080
and frequency of phone use,
link |
01:00:09.420
where they stored their phone on their body,
link |
01:00:11.460
as well as proximity of where they lived to,
link |
01:00:15.660
I guess they're called these radio frequency towers,
link |
01:00:19.140
so the base stations.
link |
01:00:20.760
And they were looking at effects of radio frequency,
link |
01:00:23.680
radiation, RFR on human hormone profiles.
link |
01:00:27.780
And they show significant decreases in cortisol.
link |
01:00:31.600
You might say, well, that might be good,
link |
01:00:33.060
but you need that morning cortisol bump
link |
01:00:35.740
in order to wake up, morning cortisol is good.
link |
01:00:38.400
But also thyroid hormones were significantly reduced.
link |
01:00:41.060
Prolactin in young females, that's definitely concerning.
link |
01:00:45.720
And testosterone levels in males and females.
link |
01:00:48.300
And so there are now quite good data showing
link |
01:00:51.340
that being close to the phone too much of the day
link |
01:00:55.220
and how close is an interesting question,
link |
01:00:58.140
or living near one of these base stations
link |
01:01:00.620
apparently can have effects on hormone profiles.
link |
01:01:04.660
And when you see a study like this, one should always ask,
link |
01:01:08.460
well, what are the other things that could also have effects
link |
01:01:11.040
on these hormone profiles, right?
link |
01:01:12.660
Because you could imagine that if you ran the same study
link |
01:01:15.660
of people that live close to a waterway
link |
01:01:17.660
or close to a highway where there's a lot of exhaust
link |
01:01:20.660
from buses and cars, you might see similar effects.
link |
01:01:23.340
So you have to take these sorts of studies
link |
01:01:24.920
with a grain of salt.
link |
01:01:25.980
But I think it's very interesting.
link |
01:01:27.220
And given that the last time I looked into these data
link |
01:01:29.620
were way back when I was a junior professor
link |
01:01:33.100
and there was like one or two studies that I could find,
link |
01:01:35.740
one of the studies pointed to increases in testosterone
link |
01:01:39.180
in rats where they had close proximity
link |
01:01:41.420
to these radio frequency radiation waves.
link |
01:01:45.300
And then in the other case,
link |
01:01:46.920
it showed decreases in testosterone.
link |
01:01:49.500
So there really wasn't any conclusion to take away
link |
01:01:52.340
from that.
link |
01:01:53.180
So now there's pretty impressive amount of data
link |
01:01:57.220
pointing to the fact that there are effects
link |
01:01:59.360
of these things on hormones.
link |
01:02:00.920
I don't know what to do with that information.
link |
01:02:02.420
I'm not going to stop using my phone,
link |
01:02:04.020
but in light of the work from Tyrone Hayes and others
link |
01:02:08.500
looking at sperm counts and looking at the decrease
link |
01:02:13.020
in testosterone levels and sperm counts and fertility
link |
01:02:16.140
over the last 20, 30 years,
link |
01:02:18.420
perhaps it's not surprising.
link |
01:02:20.840
Although there again, cell phones and smartphones
link |
01:02:24.580
have really been in prominent use
link |
01:02:26.380
mostly within the last 10 or 11 years.
link |
01:02:28.460
And so it's hard to explain all of those declines
link |
01:02:31.140
simply on the basis of cell phone use.
link |
01:02:33.740
There's some interesting effects of hormones
link |
01:02:35.540
that actually you can observe on the outside of people
link |
01:02:38.940
that tell you something about
link |
01:02:41.300
not just their level of hormones,
link |
01:02:43.240
but also about their underlying genetics.
link |
01:02:45.700
And these relate to beard growth and baldness.
link |
01:02:48.220
And it's fascinating.
link |
01:02:49.440
The molecule, the hormone,
link |
01:02:52.460
dihydrotestosterone made from testosterone
link |
01:02:56.580
is the hormone primarily responsible for facial hair,
link |
01:03:00.100
for beard growth.
link |
01:03:02.720
As well, it's the molecule,
link |
01:03:05.100
the hormone primarily responsible for lack of hair
link |
01:03:08.780
on the head for hair loss.
link |
01:03:11.340
So how does that work?
link |
01:03:12.560
Well, DHT circulates in the body
link |
01:03:15.620
and it binds to DHT receptors in the face
link |
01:03:19.060
to promote hair growth.
link |
01:03:21.340
But it binds to DHT receptors on the scalp
link |
01:03:24.440
to promote hair loss.
link |
01:03:27.300
Not incidentally,
link |
01:03:29.620
the drugs that are designed to prevent hair loss
link |
01:03:33.940
are 5-alpha reductase inhibitors.
link |
01:03:37.520
So remember 5-alpha reductase from the huevadosis?
link |
01:03:40.140
Well, the people that discovered the huevadosis
link |
01:03:42.540
went on to do a lot of research
link |
01:03:44.260
on the underlying biochemistry
link |
01:03:46.120
of this really interesting molecule, dihydrotestosterone.
link |
01:03:49.540
They identified 5-alpha reductase
link |
01:03:51.760
and 5-alpha reductase inhibitors
link |
01:03:55.340
are the basis of most of the anti-hair loss treatments
link |
01:03:59.140
that are out there.
link |
01:04:00.700
And so there are some interesting things here.
link |
01:04:02.300
First of all, the side effect profiles
link |
01:04:05.040
of those treatments for hair loss
link |
01:04:08.100
are quite severe in many individuals.
link |
01:04:10.240
Remember DHT is the primary androgen for libido,
link |
01:04:13.820
for strength and connective tissue repair,
link |
01:04:17.540
for aggression,
link |
01:04:19.940
even if that aggression of course is held in check,
link |
01:04:22.600
but just sort of ambition and aggression
link |
01:04:24.540
is related to dopamine,
link |
01:04:25.620
but within the testosterone pathway,
link |
01:04:27.980
less so pure testosterone,
link |
01:04:30.100
although pure testosterone has its effects,
link |
01:04:31.860
but DHT is at least in primate species including humans
link |
01:04:36.380
is the dominant androgen
link |
01:04:38.080
for most of those sorts of effects.
link |
01:04:40.640
And if you look at somebody,
link |
01:04:43.560
everyone can predict whether or not
link |
01:04:46.060
they're going to go bald based on looking at their,
link |
01:04:48.300
we're always taught our mother's father.
link |
01:04:50.260
So if your mother's father was bald,
link |
01:04:52.620
there's a higher probability that you're going to go bald.
link |
01:04:56.420
The pattern of DHT receptors on the scalp
link |
01:04:58.960
will dictate whether or not
link |
01:04:59.860
you're going to go bald everywhere
link |
01:05:01.560
or just in the front or so called crown type baldness.
link |
01:05:05.220
And the density of the beard
link |
01:05:06.800
tells you about the density of DHT receptors.
link |
01:05:08.920
Now this varies by background, by genetic background.
link |
01:05:13.180
And actually around the world nowadays,
link |
01:05:15.260
because people travel and people form couples
link |
01:05:18.100
and have kids with so many different people
link |
01:05:20.980
of different mixed cultures,
link |
01:05:22.420
you're seeing this starting to disappear.
link |
01:05:23.860
But there are areas of the world
link |
01:05:26.080
where all the men seem to be,
link |
01:05:28.740
have the same pattern of baldness,
link |
01:05:30.020
like a strip of baldness down the center
link |
01:05:31.780
with hair still on the sides and full beards.
link |
01:05:34.060
That's because these patterns of DHT receptors
link |
01:05:37.180
are genetically determined.
link |
01:05:39.020
Elsewhere, testosterone levels can still be very high.
link |
01:05:42.740
DHT levels in the blood can be very high.
link |
01:05:45.560
And yet people will have very light beards or no beards.
link |
01:05:48.300
And that's because they don't have
link |
01:05:49.940
a lot of DHT receptors in the face.
link |
01:05:52.260
And still other cultures,
link |
01:05:53.420
you'll see people with huge beards,
link |
01:05:55.980
tons of beard grow like their beards
link |
01:05:57.180
are growing all the way up to their eyes
link |
01:05:58.500
and they have huge heads of hair.
link |
01:05:59.780
And that's because they have a lot of DHT receptors
link |
01:06:01.460
on the face and not on the scalp.
link |
01:06:03.840
So there are a lot of effects of DHT
link |
01:06:06.260
that you can just see in male phenotypes.
link |
01:06:09.380
And it's interesting that these hair loss drugs
link |
01:06:12.260
that are, or to prevent hair loss drugs
link |
01:06:15.920
are directly aimed at preventing the conversion
link |
01:06:19.900
of testosterone into dihydrotestosterone.
link |
01:06:22.860
And that's why they, to some extent prevent hair loss,
link |
01:06:25.960
but also to some extent have a bunch of side effects
link |
01:06:29.380
that are associated with low DHT.
link |
01:06:31.820
Along these lines, there's a particular sports supplement
link |
01:06:35.260
that a lot of people use called creatine.
link |
01:06:37.780
Creatine now, there's a lot of research
link |
01:06:39.820
showing that creatine can bring more water into the muscle.
link |
01:06:43.700
It can support strength.
link |
01:06:45.820
It does a number of other things.
link |
01:06:47.700
Might even have some important cognitive promoting,
link |
01:06:50.180
cognitive enhancement effects, although mild.
link |
01:06:53.180
The studies there show that it can be significant.
link |
01:06:56.740
Some people, not all, it's more anecdotal,
link |
01:06:59.660
report that creatine promotes hair loss.
link |
01:07:03.060
It differs by individual.
link |
01:07:04.540
For some people that's true, for others, no.
link |
01:07:07.340
But yes, it does appear based on the studies
link |
01:07:09.620
I was able to find on PubMed
link |
01:07:10.920
that creatine does promote 5-alpha reductase activity
link |
01:07:15.300
and therefore the conversion of testosterone
link |
01:07:17.420
into dihydrotestosterone.
link |
01:07:19.140
And so it makes sense that it might promote
link |
01:07:21.760
some degree of hair loss, as well as beard growth,
link |
01:07:24.980
as well as the other effects of DHT.
link |
01:07:28.260
I recall in junior high school and middle school,
link |
01:07:31.380
going home one summer, it was seventh grade,
link |
01:07:33.140
coming back in the eighth grade,
link |
01:07:34.100
and a kid that I knew that I was friends with
link |
01:07:36.000
went from being like a young kid to,
link |
01:07:38.380
he was like a grown man, he had a full beard.
link |
01:07:40.400
It was amazing.
link |
01:07:41.240
It was like he would completely transform.
link |
01:07:42.780
I mean, puberty, as I've said before,
link |
01:07:44.420
is without a doubt the most accelerated
link |
01:07:48.220
rate of development that we will go through
link |
01:07:50.180
at any point in our lives, even faster than infancy,
link |
01:07:53.180
just in terms of the huge number
link |
01:07:54.900
of different cognitive changes and physical changes.
link |
01:07:58.180
Not surprisingly, that same individual
link |
01:08:00.640
was mostly or bald by his early 20s.
link |
01:08:04.820
And that's because he must've had
link |
01:08:06.000
just exceedingly high levels of DHT.
link |
01:08:08.020
I also played soccer with this kid,
link |
01:08:09.380
and he was basically like dribbling past everybody.
link |
01:08:11.180
He was like a grown man playing soccer
link |
01:08:12.520
with a bunch of little kids.
link |
01:08:13.940
Full beard, bald at 20.
link |
01:08:16.060
And so the rate of maturation,
link |
01:08:18.440
the rate of aging is very interesting.
link |
01:08:20.940
It's hard to know rate of aging.
link |
01:08:22.380
There's some genetic tests that now can allow you to do that.
link |
01:08:24.620
Things like Horvath clocks and things of that sort.
link |
01:08:27.540
Beautiful work of David Sinclair at Harvard
link |
01:08:29.500
and others has pointed to this.
link |
01:08:31.480
The speed of entry and exit from puberty might be,
link |
01:08:36.480
I'm putting it out there as a hypothesis,
link |
01:08:38.400
might be an interesting window
link |
01:08:40.100
into how fast one is going through
link |
01:08:42.640
their aging or developmental arc,
link |
01:08:44.520
because development, of course,
link |
01:08:46.020
doesn't just start at birth and end after puberty.
link |
01:08:48.440
It continues your entire life.
link |
01:08:50.560
So I think it's interesting.
link |
01:08:52.600
You will often see that people, boys and girls,
link |
01:08:57.520
I should say boys or girls,
link |
01:08:59.180
will develop secondary sexual characteristics
link |
01:09:02.640
at different rates.
link |
01:09:03.620
And sometimes it's sequential.
link |
01:09:05.320
You might see a kid will,
link |
01:09:07.720
she'll grow very tall or she'll have a big growth spurt,
link |
01:09:10.920
but then breast development will come a little bit later.
link |
01:09:13.920
And then other features will come a little bit later.
link |
01:09:16.680
You can also see this in boys.
link |
01:09:17.980
The person that I referred to earlier,
link |
01:09:19.680
my friend that developed full beard, went bald.
link |
01:09:22.800
He was also quite muscular.
link |
01:09:24.000
He's a great athlete.
link |
01:09:25.240
So he went through puberty exceedingly fast.
link |
01:09:27.400
Other people go through it more slowly.
link |
01:09:29.120
Some people will go through puberty at age 14,
link |
01:09:32.700
but they won't start to accumulate facial hair
link |
01:09:35.000
until much, much later.
link |
01:09:36.960
Or their voice will change first very early,
link |
01:09:40.040
and then they won't get the other secondary
link |
01:09:43.240
sexual characteristics until much later.
link |
01:09:45.720
And so we don't really know how that impacts
link |
01:09:48.280
or relates to overall trajectory or rate of aging,
link |
01:09:51.440
but it's an interesting thing to think about
link |
01:09:53.760
for each and every one of us.
link |
01:09:55.280
I'm going to offer you the opportunity
link |
01:09:56.720
to do an experiment today while listening to the podcast.
link |
01:10:00.200
But first I want to tell you a story about hyenas,
link |
01:10:05.540
professional baseball, and clitorises the size of penises.
link |
01:10:10.920
So when I was a graduate student at UC Berkeley,
link |
01:10:15.400
we had a professor in our department,
link |
01:10:17.740
phenomenal scientist named Steve Glickman.
link |
01:10:21.480
Steve Glickman had a colony of hyenas, spotted hyenas,
link |
01:10:26.480
that lived within caged enclosures, of course,
link |
01:10:30.540
in Tilden Park behind the UC Berkeley campus.
link |
01:10:33.180
The enclosures are actually still there.
link |
01:10:34.920
I run past there fairly often.
link |
01:10:36.960
The hyenas are no longer there.
link |
01:10:39.020
This was a federally funded field station.
link |
01:10:41.360
These animals were brought over from Africa
link |
01:10:44.600
or were bred there.
link |
01:10:46.480
And the reason why there were hyenas in Tilden Park,
link |
01:10:51.480
enclosed in Tilden Park,
link |
01:10:53.480
was because hyenas exhibit an incredible feature
link |
01:10:56.880
to their body, their hormones, and their social structure.
link |
01:11:02.040
Hyenas, unlike many species,
link |
01:11:05.640
have a situation with their genitalia
link |
01:11:08.000
where the male penis is actually smaller
link |
01:11:12.440
than the female clitoris.
link |
01:11:14.940
And I should say that the male penis itself,
link |
01:11:17.200
having seen a fair number of hyena penises,
link |
01:11:20.840
is not particularly small,
link |
01:11:22.700
which means that the hyena clitorises are extremely large.
link |
01:11:27.840
This was well-known for some time.
link |
01:11:30.220
It turns out that in these spotted hyenas,
link |
01:11:34.800
the females are dominant.
link |
01:11:37.000
So after a kill, the females will eat,
link |
01:11:39.540
then their young will eat,
link |
01:11:41.240
and then the male hyenas will eat.
link |
01:11:44.840
As well, when the female hyena gives birth,
link |
01:11:49.040
she gives birth not through the vaginal canal
link |
01:11:53.080
that we're accustomed to seeing,
link |
01:11:56.440
but through a very enlarged clitoris-like phallus,
link |
01:12:03.140
although it's not a phallus, it's a clitoris,
link |
01:12:05.680
and it literally splits open.
link |
01:12:07.680
So many fetuses die
link |
01:12:09.360
during the course of hyena development and birth.
link |
01:12:14.440
These animals have this,
link |
01:12:16.360
what could only be described
link |
01:12:17.920
as a very large sort of giant clitoris,
link |
01:12:19.960
although for a hyena, it's not giant, it's normal.
link |
01:12:22.280
And it splits open, and the baby actually comes through.
link |
01:12:25.240
The baby hyena actually comes through the tissue,
link |
01:12:29.100
and it's a very traumatic birth.
link |
01:12:31.640
A lot of tissue is torn away, et cetera.
link |
01:12:33.880
And as I mentioned, a lot of baby hyenas die.
link |
01:12:36.840
It was a mystery as to how the female hyenas have this,
link |
01:12:42.600
we'll call it masculinization,
link |
01:12:44.000
but it's really a androgen, excuse me,
link |
01:12:47.000
androgenization of the periphery of the genitalia.
link |
01:12:52.480
And it turns out through a lot of careful research
link |
01:12:55.440
done by Steve Glickman, Christine Dre, and others,
link |
01:13:00.000
that it's androstenedione,
link |
01:13:03.720
what is essentially a pro-hormone to testosterone,
link |
01:13:07.820
it's androstenedione at very high levels
link |
01:13:10.520
that's produced in female hyenas
link |
01:13:13.600
that creates this enlargement of their genitalia.
link |
01:13:16.640
So if you want to read up on androstenedione,
link |
01:13:19.280
androstenedione is made into testosterone
link |
01:13:22.020
through this enzyme, 17-beta hydroxysteroid dehydrogenase.
link |
01:13:29.320
It's a complicated pathway to pronounce.
link |
01:13:32.320
It's a fairly straightforward pathway biochemically.
link |
01:13:35.600
You may recall during the 90s and 2000s,
link |
01:13:39.240
there were a lot of performance enhancing drug scandals,
link |
01:13:42.600
in particular in major league baseball.
link |
01:13:45.040
And it was purported,
link |
01:13:47.660
although I don't know that it was ever verified,
link |
01:13:49.660
but it was purported that the major
link |
01:13:53.020
performance enhancing drug of abuse at that time,
link |
01:13:55.960
in particular players whose names we won't mention,
link |
01:13:58.000
but you can Google it if you want to find out,
link |
01:14:00.380
was androstenedione.
link |
01:14:01.760
And I actually recall long ago
link |
01:14:03.480
when you could buy androstenedione in the health food stores.
link |
01:14:07.540
And so it was sold over the counter.
link |
01:14:10.080
So a lot's changed since then,
link |
01:14:13.120
but it's interesting that these hyenas
link |
01:14:15.360
with these highly androgenized genitalia
link |
01:14:20.440
accomplish that through high levels of androstenedione
link |
01:14:24.080
in the females.
link |
01:14:24.920
Now, if that's unusual,
link |
01:14:27.160
what might be even more unusual
link |
01:14:28.960
is that a graduate student that I was working with
link |
01:14:31.400
at the time, alongside, we didn't share research.
link |
01:14:34.220
Her name was Nicola Sipka.
link |
01:14:36.520
She is actually a trained animal behavioral expert.
link |
01:14:40.360
She had trained ferrets for that show, The Beastmaster,
link |
01:14:43.760
and she would train wolves for television shows
link |
01:14:46.680
and was a dog trainer.
link |
01:14:47.760
She had these two large dogs that,
link |
01:14:49.440
unlike my dog, would actually listen to her
link |
01:14:51.320
when she would give them commands.
link |
01:14:53.680
A remarkable scientist.
link |
01:14:55.080
She was studying a species of mole
link |
01:14:58.340
that also lived in Tilden Park.
link |
01:14:59.860
People are going to start to wonder about Tilden Park.
link |
01:15:01.720
What's in Tilden Park?
link |
01:15:03.040
But this particular mole that lived there
link |
01:15:06.640
had testes for part of the year
link |
01:15:09.060
and had the capacity to transdifferentiate its testes
link |
01:15:12.520
into ovaries in order to balance out the ratio
link |
01:15:15.400
of males and females in the population
link |
01:15:17.260
to keep reproduction at appropriate levels
link |
01:15:20.440
for that certain population.
link |
01:15:22.260
So some animals are actually able to adjust
link |
01:15:26.200
whether or not they have androgenized or estrogenized gonads
link |
01:15:32.080
in order to adjust the ratios of offspring
link |
01:15:36.840
or the males and females in there for promote offspring.
link |
01:15:39.840
And the last little anecdote about this,
link |
01:15:41.960
which is also published in the scientific literature,
link |
01:15:45.120
which is weird, but I do find interesting.
link |
01:15:47.360
Hormones are so fascinating.
link |
01:15:48.680
They're just incredible to me,
link |
01:15:50.480
is going back to the marijuana plant.
link |
01:15:54.880
The marijuana plant has these estrogenic properties.
link |
01:15:58.860
And I asked a plant biologist whether or not
link |
01:16:02.240
this was unusual.
link |
01:16:03.380
And I asked, because there's all this stuff out there
link |
01:16:07.500
about, oh, soy does this,
link |
01:16:09.300
and these plants are highly estrogenic, et cetera,
link |
01:16:12.940
although we should probably point out
link |
01:16:13.920
that a lot of factory meats are also estrogenic.
link |
01:16:15.820
So this isn't a meat versus plants thing.
link |
01:16:18.020
But this plant biologist told me,
link |
01:16:19.280
oh yeah, there are plants that make
link |
01:16:22.640
what is essentially the equivalent of testosterone,
link |
01:16:26.000
like pine pollen, it looks a lot like testosterone.
link |
01:16:28.520
And there are other plants that make
link |
01:16:30.340
what is essentially estrogen.
link |
01:16:33.020
And I said, well, why would they do that?
link |
01:16:34.740
And plants, at least as far as I know,
link |
01:16:37.620
don't have a consciousness.
link |
01:16:38.580
They don't have a brain.
link |
01:16:39.540
They don't have neurons even.
link |
01:16:41.180
But his answer was fascinating.
link |
01:16:45.220
He said that one of the reasons
link |
01:16:48.020
why some plants have evolved this capacity
link |
01:16:51.080
to increase estrogen levels in animals that smoke,
link |
01:16:56.420
not smoke it, but then animals that consume them,
link |
01:16:58.680
I'm guessing that animals aren't smoking marijuana,
link |
01:17:00.540
although, I don't know, send me the paper
link |
01:17:03.060
if you've heard of this,
link |
01:17:04.000
is that plants have figured out ways,
link |
01:17:06.840
they've adapted ways to push back on populations
link |
01:17:10.060
of rodents and other species of animals that eat them.
link |
01:17:13.060
So plants are engaged in a kind of plant to animal warfare
link |
01:17:17.660
where they increase the estrogen
link |
01:17:19.340
of the males in that population to lower the sperm counts
link |
01:17:22.140
to keep those populations clamped at certain levels
link |
01:17:25.420
so that those plants can continue to flourish
link |
01:17:28.300
even if those animals are reproducing very robustly.
link |
01:17:33.140
And I find this just fascinating.
link |
01:17:35.180
And hormones, therefore,
link |
01:17:37.740
aren't just impacting tissue growth and development
link |
01:17:41.860
within the individual and between the mother.
link |
01:17:44.340
Remember, the placenta is an endocrine organ
link |
01:17:46.380
and the offspring.
link |
01:17:47.340
But plants and animals are in this communication.
link |
01:17:49.840
And today we're in this communication.
link |
01:17:51.360
I'm telling you that there are certain herbicides
link |
01:17:53.540
that humans are using for which there's very good data
link |
01:17:56.020
are disrupting the endocrine pathways.
link |
01:17:59.360
And so it's fascinating that humans and other animals
link |
01:18:03.140
were always in this interplay with plants
link |
01:18:05.340
and the other things in our environment.
link |
01:18:07.900
And hormones and adjusting the hormone levels
link |
01:18:10.940
of animals and plants is one way in which the environment
link |
01:18:14.100
kind of pushes back or pushes forward, if you will,
link |
01:18:17.180
in terms of promoting their wellbeing and longevity
link |
01:18:20.740
as well as you trying to promote
link |
01:18:21.960
your wellbeing and longevity.
link |
01:18:23.800
If anyone wants to see the incredible paper
link |
01:18:25.940
by Steve Glickman and colleagues,
link |
01:18:27.900
it was published in the Prosthenes of the National Academy
link |
01:18:30.020
first in 1987.
link |
01:18:32.260
That's Glickman et al.
link |
01:18:33.380
That was the hypothesis that it was androstenedione.
link |
01:18:35.860
And then if you just Google Glickman Hyenas Science Magazine,
link |
01:18:41.100
there's a beautiful cover article
link |
01:18:43.620
and feature all about that important discovery.
link |
01:18:45.820
It's a fascinating one.
link |
01:18:47.220
And I should mention also that those discoveries,
link |
01:18:50.300
both the moles and the hyenas weren't just impactful
link |
01:18:54.260
for the world of animal behavior and endocrinology.
link |
01:18:56.460
They've also strongly impacted understanding
link |
01:18:59.460
of conditions that show up in the clinic,
link |
01:19:01.620
which we haven't talked about today,
link |
01:19:03.580
which is actually pseudo hermaphroditism.
link |
01:19:06.040
Occasionally babies will be born where it is unclear
link |
01:19:09.140
if they are boys or girls based on the genitalia.
link |
01:19:13.220
And this has a very important ethical and other issues.
link |
01:19:17.900
Do you raise them as a boy or a girl?
link |
01:19:19.980
It's not super uncommon for this to happen.
link |
01:19:23.580
And there've been terrible cases where people have gone
link |
01:19:27.160
against the chromosomal sex and the person was very unhappy
link |
01:19:32.780
with the choice that their parents had made for them.
link |
01:19:34.900
There were also cases where they've gone
link |
01:19:36.620
with the chromosomal sex and the person was very happy
link |
01:19:39.100
about the outcome.
link |
01:19:39.940
There've been cases where they've been treated
link |
01:19:41.340
with hormones and there've been cases
link |
01:19:43.100
where they have not been treated with hormones.
link |
01:19:44.620
It's a complicated literature and it has to be sorted out
link |
01:19:50.860
on kind of a case by case basis,
link |
01:19:52.380
but it is something that does happen.
link |
01:19:54.060
And the studies on androstenedione and hyenas
link |
01:19:56.940
and in these very interesting moles,
link |
01:19:59.860
pseudo hermaphroditic moles that live in Tilden Park
link |
01:20:02.820
have impacted not just the science,
link |
01:20:05.040
but the therapeutics around those important issues.
link |
01:20:08.260
So now last but not least,
link |
01:20:10.520
I want to discuss the effects of hormones
link |
01:20:13.860
while you and I were separately in utero
link |
01:20:18.580
and the effects that that had on who we are,
link |
01:20:24.060
who we select as mates, so mate choice, sexual preference,
link |
01:20:28.980
and all other aspects
link |
01:20:31.620
of what you would call sexual development.
link |
01:20:35.380
Now, this is something that's gotten a lot of popular press
link |
01:20:38.620
and it has to do with how exposure to androgens
link |
01:20:42.260
in particular while we were in utero impacted
link |
01:20:46.380
whether or not people report as homosexual, heterosexual,
link |
01:20:50.180
identify as male or female.
link |
01:20:52.720
I'm very familiar with this work
link |
01:20:54.220
because I was a graduate student in the department
link |
01:20:56.100
that first published this work
link |
01:20:57.300
and I'm an author on the paper.
link |
01:20:59.580
I was not the main driver of the work,
link |
01:21:01.620
but I was involved in the work
link |
01:21:03.540
and I certainly know the people that did this work.
link |
01:21:07.780
First, it starts with a story.
link |
01:21:10.680
There was a researcher who's still going now.
link |
01:21:13.760
His name is Dennis McFadden.
link |
01:21:16.460
I believe he was at UT Austin back then
link |
01:21:19.060
and he was studying the auditory system
link |
01:21:22.220
and people would come into his clinic
link |
01:21:23.540
and he would, or his laboratory,
link |
01:21:25.700
and he would look at hearing
link |
01:21:28.560
and he would explore different aspects
link |
01:21:30.120
of what they call the psychophysics of hearing
link |
01:21:31.740
and understanding hearing thresholds
link |
01:21:33.300
and frequency thresholds.
link |
01:21:34.820
And he made several observations
link |
01:21:38.060
and those observations were that young males
link |
01:21:43.060
tended to have what are called autoacoustic emissions
link |
01:21:47.060
more often than young females did.
link |
01:21:49.780
Autoacoustic emissions, as the name suggests,
link |
01:21:52.180
are the ears actually making sounds.
link |
01:21:54.620
Now, these sounds have to be picked up
link |
01:21:56.100
by a special apparatus
link |
01:21:57.420
because they can hear into that frequency,
link |
01:21:58.880
but it turns out that your ears
link |
01:22:00.220
don't just take sound waves
link |
01:22:02.440
and convert them into these things,
link |
01:22:04.220
this thing we call hearing,
link |
01:22:05.280
but they also, in some cases, make sounds.
link |
01:22:07.500
So your ears are making sounds, strange, right?
link |
01:22:10.360
So it turns out that there's a sex difference
link |
01:22:14.420
in autoacoustic emissions.
link |
01:22:16.740
Turns out also that people that self-report as lesbians,
link |
01:22:21.820
they also have autoacoustic emissions
link |
01:22:24.180
significantly more than females
link |
01:22:26.460
that don't self-report as lesbian.
link |
01:22:29.460
And Dennis noticed this and published this,
link |
01:22:33.520
and it was an important discovery
link |
01:22:35.340
because it was one of the first discoveries
link |
01:22:38.360
that pointed to the fact that there are sex differences
link |
01:22:44.140
in biology that are independent of sex.
link |
01:22:46.900
I mean, this is hearing in autoacoustic emissions.
link |
01:22:49.140
And just to really illustrate what the former problem was
link |
01:22:54.100
and why this study was so important,
link |
01:22:56.600
a lot of people had explored, for instance,
link |
01:22:58.640
whether or not homosexuals had lower testosterone,
link |
01:23:03.840
for instance, in males.
link |
01:23:04.740
And actually the result often was the opposite,
link |
01:23:06.740
that gay men or men that self-report as gay
link |
01:23:09.980
often had much higher testosterone.
link |
01:23:12.420
And those studies then became controversial
link |
01:23:15.040
because people said, well,
link |
01:23:16.860
sexual behavior can relate to testosterone, et cetera.
link |
01:23:19.460
And so it became very controversial.
link |
01:23:21.220
And then there were some studies
link |
01:23:22.660
that attempted to look at the equivalent phenomenon
link |
01:23:25.500
in people that self-report as lesbian
link |
01:23:28.100
or self-report as heterosexual.
link |
01:23:30.260
And so it became very complicated,
link |
01:23:31.820
but this was an identification of a phenomenon,
link |
01:23:36.160
autoacoustic emissions, that was independent of anything
link |
01:23:39.020
that had to do with sexual or even social behavior.
link |
01:23:43.140
1998 rolls around,
link |
01:23:45.820
and I'm a graduate student at UC Berkeley
link |
01:23:48.900
and a guy by the name of Mark Breedlove,
link |
01:23:50.900
kind of an ironic name given that he worked
link |
01:23:54.000
and still works on sexual dimorphism in the brain
link |
01:23:57.320
and in the spinal cord and nervous system.
link |
01:23:59.380
And Mark, who's a phenomenal scientist,
link |
01:24:03.260
comes running down the hall, I'll never forget this,
link |
01:24:05.600
and he said, give me your hands.
link |
01:24:06.980
I was like, give me your hands.
link |
01:24:08.220
And he pulls out a ruler and he starts measuring my fingers.
link |
01:24:10.560
And he takes down a couple of measurements
link |
01:24:11.860
and then he goes away.
link |
01:24:13.620
And I'm like, what was that?
link |
01:24:15.500
Well, I was in a course that Mark was teaching
link |
01:24:18.340
at that point.
link |
01:24:19.820
And soon after we did a study that Mark directed,
link |
01:24:26.060
exploring the finger length ratios,
link |
01:24:29.020
and I'll explain what those are,
link |
01:24:30.660
of males and females
link |
01:24:34.020
and people that self-reported
link |
01:24:35.780
as homosexual or heterosexual.
link |
01:24:38.480
So let's just get to the basic,
link |
01:24:40.780
what we'll call sex differences first.
link |
01:24:43.520
These are averages I want to point out.
link |
01:24:45.380
Anytime you get into this kind of topic,
link |
01:24:46.980
people assume it's causal, but it's not causal.
link |
01:24:49.340
These are averages that I'm about to report.
link |
01:24:52.820
It is the case that the ratio
link |
01:24:55.520
of what's called the D2 to D4 digits.
link |
01:24:57.980
So the D2 is your index finger.
link |
01:24:59.860
So your thumb is D1,
link |
01:25:01.100
then D2 would be your index finger that you would point with.
link |
01:25:03.580
Middle finger is D3, which you whatever with.
link |
01:25:06.300
And then D4 is the so-called ring finger, okay?
link |
01:25:10.500
And D5 is the pinky.
link |
01:25:12.860
It is the case that the D2 to D4 ratio
link |
01:25:18.060
is greater in self-reported females than it is in males.
link |
01:25:23.620
What does that mean?
link |
01:25:24.460
It means that digit D2 and D4 are more similar in length
link |
01:25:29.940
in females than in males.
link |
01:25:31.700
And the effect is particularly, excuse me,
link |
01:25:34.760
pronounced on the right hand, although not always, okay?
link |
01:25:39.180
And it does not have to do with handedness.
link |
01:25:41.420
This D2 to D4 difference has to be measured correctly.
link |
01:25:45.820
You can't just look at somebody's hands and say,
link |
01:25:47.680
oh, their ring finger and index finger are very similar
link |
01:25:51.960
and therefore they are female
link |
01:25:55.640
or they were exposed to very little testosterone in utero.
link |
01:25:58.880
You can't look at somebody
link |
01:26:00.260
and see that their index finger is much shorter
link |
01:26:02.200
than their ring finger and say,
link |
01:26:04.040
oh, they must've been exposed to a lot of androgen.
link |
01:26:06.740
You have to actually measure it
link |
01:26:07.900
and you have to measure it correctly.
link |
01:26:09.860
You have to measure it from the base of the finger
link |
01:26:12.380
where there's that first crease all the way to the tip
link |
01:26:15.220
past the, you can't include the fingernails
link |
01:26:17.660
if you're growing fingernails,
link |
01:26:18.580
it would be logical here, folks.
link |
01:26:21.620
So you can't normally see it from the back of the hand,
link |
01:26:24.940
although I don't know if this will show up here,
link |
01:26:26.900
but if you look at the back of the hand,
link |
01:26:29.260
sometimes you can see it.
link |
01:26:30.580
In my case, for instance, let me see if I can do this.
link |
01:26:33.980
So my D4 is a little bit longer than my D2.
link |
01:26:37.720
In some people it's more pronounced
link |
01:26:39.380
and that's on my right hand.
link |
01:26:40.300
On the other hand,
link |
01:26:41.120
the difference actually is far less pronounced.
link |
01:26:42.620
It's a little bit pronounced there, but not so much.
link |
01:26:47.160
So that's sort of the typical ratio that you would see.
link |
01:26:51.600
Turns out that in mice and in humans,
link |
01:26:54.740
the more androgen that you were exposed to in utero,
link |
01:27:00.140
the smaller the D4, D2 ratio,
link |
01:27:01.980
meaning that the ring finger tends to be slightly longer
link |
01:27:05.780
than the pointer finger.
link |
01:27:07.460
And in females,
link |
01:27:08.440
because they're exposed to less androgen in utero typically,
link |
01:27:13.120
then those fingers tend to be more equal in length.
link |
01:27:15.320
And these are subtle differences and these are averages.
link |
01:27:18.040
I invite you to look up the paper.
link |
01:27:19.920
This was published in Nature in 2000
link |
01:27:21.800
and it's been replicated six times.
link |
01:27:26.400
Now here's where it gets even more interesting
link |
01:27:30.020
and potentially precarious.
link |
01:27:31.520
So we're going to step cautiously here.
link |
01:27:34.760
If you look at the finger length ratios
link |
01:27:37.260
of men that self-report as homosexual,
link |
01:27:40.640
they have either the typical male pattern
link |
01:27:43.320
of D2 to D4 ratio
link |
01:27:45.600
or a hyper masculinized D4 to D2 ratio.
link |
01:27:49.200
Now this can't be something that's established
link |
01:27:51.600
or modified by behavior.
link |
01:27:53.680
This has to be something that was established in utero.
link |
01:27:56.040
And in fact, it's present at birth, okay?
link |
01:28:00.480
So it completely divorces the interactions
link |
01:28:03.720
between hormones and behavior.
link |
01:28:05.280
And that's an important theme that we've been talking about
link |
01:28:07.160
and we're going to talk about even more next episode
link |
01:28:08.900
is that hormones impact behavior
link |
01:28:10.400
but behavior also impact hormones.
link |
01:28:12.100
But this is a case of hormones impacting
link |
01:28:14.860
what really should be considered
link |
01:28:16.340
a primary sexual characteristic
link |
01:28:18.780
because it doesn't show up in puberty.
link |
01:28:20.240
It shows up before puberty.
link |
01:28:21.400
It's actually established in utero.
link |
01:28:23.880
And in people that self-reported lesbians,
link |
01:28:27.040
and I remember going out there and collecting these data
link |
01:28:29.160
with the collaborators on this work.
link |
01:28:31.860
Again, I wasn't the main driver on the work
link |
01:28:33.620
but I participated in some of the analysis.
link |
01:28:36.200
People that self-report as lesbians
link |
01:28:38.160
also tend to have a smaller D2 to D4 ratio.
link |
01:28:43.560
So this is consistent with the autocoustic emissions study
link |
01:28:46.400
that Dennis McFadden had published.
link |
01:28:48.200
And it points to the fact that early exposure to androgens
link |
01:28:51.860
may have an impact,
link |
01:28:54.600
not just on androgenization of the body plan
link |
01:28:59.540
but also separately on sexual preference.
link |
01:29:04.660
Now, this raises all sorts of interesting questions
link |
01:29:06.940
about biological basis of sexual preference.
link |
01:29:08.960
I'll tell you about another study,
link |
01:29:10.800
a guy named Simon LeVay who was at UCLA
link |
01:29:13.780
who trained under Hubel and Wiesel.
link |
01:29:16.560
If any of you remember early episodes on plasticity,
link |
01:29:18.720
David Hubel and Torrance and Wiesel,
link |
01:29:20.280
my scientific great-grandparents won the Nobel Prize
link |
01:29:22.860
for discovery of critical periods for brain plasticity.
link |
01:29:26.620
They defined some of the most important aspects
link |
01:29:28.600
of how we see and brain plasticity.
link |
01:29:31.600
Simon LeVay trained with them.
link |
01:29:33.840
And then Simon went on to discover
link |
01:29:36.300
that in the brains of people that self-report homosexual,
link |
01:29:40.620
there is a brain difference.
link |
01:29:42.400
And the brain difference is in an area
link |
01:29:43.960
called the interstitial nucleus
link |
01:29:45.520
of the anterior hypothalamus.
link |
01:29:47.560
So it's the INAH.
link |
01:29:50.440
And so there are published reports
link |
01:29:54.720
that was published in Science.
link |
01:29:56.340
The other work I refer to as published in Nature
link |
01:29:58.120
and then replicated no fewer than six times
link |
01:30:00.680
and the McFadden results that point
link |
01:30:02.600
to strong biological correlates of mate choice
link |
01:30:09.480
of sexual preference.
link |
01:30:11.560
And these tie directly to things like androgenization
link |
01:30:17.420
or estrogenization, meaning we could call it maleness
link |
01:30:20.280
or femaleness, but that's sort of tricky territory
link |
01:30:22.600
because of the way that we described the huge range
link |
01:30:24.700
in which sex can be defined earlier.
link |
01:30:27.000
So if you want to measure D2, D4 ratio, you're welcome to,
link |
01:30:31.800
but you also have to understand
link |
01:30:33.960
that it's not predictive of anything, right?
link |
01:30:36.720
It's just a window into the possible androgen exposure
link |
01:30:40.000
that you had early in life.
link |
01:30:41.560
There are plenty of men who report themselves
link |
01:30:44.680
as heterosexual who are out there
link |
01:30:46.360
who have similar or have D2, D4 ratios to females.
link |
01:30:50.320
And there are plenty of females whose index fingers
link |
01:30:52.800
are shorter than their ring fingers
link |
01:30:54.480
and they're perfectly happy
link |
01:30:55.760
or they say they're perfectly happy
link |
01:30:57.540
and we are inclined to believe them being heterosexual.
link |
01:31:00.120
So there's variation.
link |
01:31:01.080
In fact, Mark tells a really good joke.
link |
01:31:04.400
If you want to know whether or not somebody is homosexual
link |
01:31:07.240
or heterosexual, simply look at their hands,
link |
01:31:10.780
look at their D2, D4 ratio and guess heterosexual
link |
01:31:15.240
and you'll be right 96% of the time
link |
01:31:17.520
because 96% of the time people report themselves
link |
01:31:20.560
as heterosexual on average, those numbers might be changing.
link |
01:31:23.680
So the joke really is a joke on science
link |
01:31:26.120
because that falls within the realm
link |
01:31:28.420
of statistical significance
link |
01:31:29.960
and yet it really illustrates the fact
link |
01:31:31.820
that none of this is causal,
link |
01:31:33.800
but it's nonetheless very interesting
link |
01:31:35.600
because it means that hormones are organizing
link |
01:31:37.840
the brain early in development
link |
01:31:39.280
in ways that can potentially impact same
link |
01:31:42.840
or opposite sex partner choice later in life.
link |
01:31:45.940
Now, of course, there are other things
link |
01:31:47.080
that can impact opposite sex
link |
01:31:48.800
or same sex partner choice later in life.
link |
01:31:51.200
The study did not look at people who reported bisexual.
link |
01:31:54.600
There hasn't been a lot of studies on that yet.
link |
01:31:57.760
One thing that's very interesting
link |
01:31:59.400
for which there are some good scientific data
link |
01:32:01.960
but there's also some controversy
link |
01:32:03.720
is that it appears that the probability
link |
01:32:07.600
of a male human self-reporting as homosexual
link |
01:32:11.840
increases with the number of older brothers that he has.
link |
01:32:16.400
Now, that doesn't mean if you have an older brother
link |
01:32:18.240
even if you have 10 older brothers
link |
01:32:19.800
that you are sure to self-report as homosexual,
link |
01:32:22.860
but statistically it becomes more likely
link |
01:32:26.840
that somebody will with each successive older brother
link |
01:32:30.360
that they have.
link |
01:32:31.520
And the idea that's starting to emerge
link |
01:32:33.160
in the developmental neuroendocrinology landscape
link |
01:32:37.120
is that there's a record within the mother
link |
01:32:41.120
of how many male fetuses she's carried
link |
01:32:43.400
because male fetuses are secreting certain things,
link |
01:32:46.360
dihydrotestosterone, other things
link |
01:32:48.680
that can feed back onto the genome.
link |
01:32:51.840
So these could be epigenomic effects
link |
01:32:53.360
or onto the placenta itself
link |
01:32:55.700
so that there's a higher probability
link |
01:32:57.640
in subsequent pregnancies
link |
01:32:59.480
that offspring will self-report as homosexual.
link |
01:33:02.880
So it's a fascinating area of biology.
link |
01:33:05.040
And as you've noticed today,
link |
01:33:06.500
none of this deals with the current controversies
link |
01:33:09.680
around gender and how many genders and sex, et cetera.
link |
01:33:12.980
That's a separate conversation that is by definition
link |
01:33:16.460
grounded in the kind of concepts
link |
01:33:18.260
we've been talking about today
link |
01:33:19.680
and needs to take place taking into consideration
link |
01:33:22.760
all of the aspects of sex and the effects of hormones
link |
01:33:26.200
both on the body, on the brain.
link |
01:33:28.560
We didn't talk a lot about spinal cord
link |
01:33:30.000
but we will in the next episode
link |
01:33:32.120
but we can just say on the brain and the periphery
link |
01:33:34.720
early effects, late effects, acute effects
link |
01:33:38.080
meaning effects that are very fast
link |
01:33:40.160
of levels of hormones going up or down
link |
01:33:42.240
something that absolutely happens
link |
01:33:43.700
during and across the menstrual cycle
link |
01:33:46.340
as well as long-term effects
link |
01:33:47.920
like the effects of these hormones on gene expression.
link |
01:33:51.680
So today, as always, we weren't able to cover
link |
01:33:55.480
all things related to sex and hormones
link |
01:33:59.640
and sexual differentiation or development.
link |
01:34:02.820
There's no way we could
link |
01:34:04.120
but we have covered a lot of material.
link |
01:34:06.320
We talked about some effects of environmental toxins.
link |
01:34:10.360
We talked about potential effects of cell phone radiation
link |
01:34:12.920
something I never thought that I would be talking about
link |
01:34:15.720
especially not in a podcast
link |
01:34:17.380
but for which there are interesting emerging data.
link |
01:34:19.420
We talked about considerations about evening primrose oil
link |
01:34:23.340
and its estrogenic effects, about creatine
link |
01:34:25.460
and its pro DHT effects, about cannabis alcohol
link |
01:34:29.140
about plants exerting warfare on animals
link |
01:34:31.760
by increasing aromatase
link |
01:34:33.160
the conversion of testosterone to estrogen.
link |
01:34:35.160
We talked about hyenas with giant clitorises
link |
01:34:37.360
and we talked about moles that can convert
link |
01:34:40.200
from having ovaries to testicles.
link |
01:34:43.520
And throughout this Costello has been snoring nonstop.
link |
01:34:46.480
He missed all of it
link |
01:34:48.000
although he might be learning it in his sleep
link |
01:34:50.300
for all I know.
link |
01:34:51.840
And I do understand it's a lot of information
link |
01:34:54.960
a lot of detail as always, I just want to remind you
link |
01:34:57.320
you don't have to absorb all the information at once.
link |
01:35:00.040
Next episode, we are going to be talking about
link |
01:35:02.640
the science of sex, the verb, actual reproduction.
link |
01:35:06.720
We're also going to be talking about effects of hormones
link |
01:35:09.480
on various aspects of behavior
link |
01:35:11.700
and ways to modulate hormones
link |
01:35:14.160
through the use of behavior, supplementation.
link |
01:35:19.240
Also, we'll touch on diet and nutrition a bit.
link |
01:35:22.040
And we're going to talk about interactions
link |
01:35:24.040
between those things and behavior
link |
01:35:26.120
as they relate to important themes
link |
01:35:28.240
like sex and reproduction, like workplace performance
link |
01:35:32.280
like motivation and drive, and even anxiety.
link |
01:35:34.860
There's a very interesting relationship
link |
01:35:36.840
between hormones and anxiety
link |
01:35:39.200
and the desire to explore novelty.
link |
01:35:42.400
So just remember as we go forward
link |
01:35:44.240
that hormones affect behavior
link |
01:35:46.400
and behavior affects hormones
link |
01:35:48.760
but that doesn't mean that cutting off your index finger
link |
01:35:51.000
will increase your testosterone.
link |
01:35:53.120
Many of you have asked how you can help support the podcast
link |
01:35:55.920
and we thank you for the question.
link |
01:35:57.700
There are several ways to do that.
link |
01:35:59.020
The first one is to subscribe on YouTube.
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01:36:01.080
If you haven't subscribed to the YouTube channel already
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01:36:03.040
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01:36:04.280
As well, please hit the subscribe button
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01:36:06.040
so you're sure not to miss any of the episodes.
link |
01:36:08.400
We do release episodes every Monday
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01:36:10.520
but we also occasionally release short clips in between.
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01:36:14.400
As well, if you could subscribe on Apple and or Spotify
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01:36:17.720
that's very helpful.
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01:36:18.800
And on Apple, you have the opportunity to leave us
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01:36:20.960
up to a five-star review and to leave a comment.
link |
01:36:24.360
On YouTube, please do leave us comments and suggestions
link |
01:36:27.240
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link |
01:36:28.560
We really appreciate the feedback
link |
01:36:30.100
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link |
01:36:32.200
Also ask us any questions you have about the material.
link |
01:36:35.120
Those questions help guide our office hours,
link |
01:36:37.780
this discussion about your questions
link |
01:36:39.440
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01:36:40.840
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01:36:43.420
Also, if you could tell people about the podcast
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01:36:45.500
please tell your family, your friends, your coworkers
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01:36:48.040
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link |
01:36:50.460
That really helps us get the word out.
link |
01:36:52.700
As well, if you're interested in supplements
link |
01:36:55.180
we've partnered with Thorne, T-H-O-R-N-E.
link |
01:36:58.860
And we've partnered with Thorne
link |
01:36:59.940
because Thorne has the highest level of stringency
link |
01:37:02.400
with respect to the ingredients
link |
01:37:04.120
that they put in their products
link |
01:37:05.800
as well as the precise amounts of those contents.
link |
01:37:09.480
A lot of supplement brands out there
link |
01:37:10.840
claim to have X amount of some supplement
link |
01:37:13.480
but then when people have measured
link |
01:37:15.520
the amount in capsules and tablets
link |
01:37:17.000
it's turned out to be very different.
link |
01:37:18.120
Thorne is very precise about this.
link |
01:37:19.520
They partnered with important and stringent institutions
link |
01:37:23.160
like the Mayo Clinic, all the major sports teams.
link |
01:37:25.260
So that's why we partnered with Thorne.
link |
01:37:27.300
If you want to try any of Thorne's products
link |
01:37:29.160
if you want to see what I take, you can go to Thorne
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01:37:31.380
that's thorne.com slash the letter U slash Huberman.
link |
01:37:36.760
And if you do that
link |
01:37:37.600
you can see any of the products that I take
link |
01:37:39.080
you can get 20% off any of those
link |
01:37:41.500
as well as 20% off any of the other products
link |
01:37:43.800
that Thorne makes.
link |
01:37:45.040
So that's thorne.com slash U slash Huberman.
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01:37:48.720
Please also check out our sponsors
link |
01:37:50.440
check out the sponsor links.
link |
01:37:51.680
That's perhaps the best way to support us.
link |
01:37:54.400
And of course, I want to point out
link |
01:37:56.060
that any of the ways that support us
link |
01:37:58.160
whether or not they are cost-free
link |
01:37:59.440
like subscribing and leaving comments
link |
01:38:00.940
or whether or not you're interested in the products
link |
01:38:03.200
that I've referred to, those all help us.
link |
01:38:05.840
And so we really appreciate it.
link |
01:38:07.880
So once again, I want to thank you
link |
01:38:09.520
for embarking on this journey through neuroscience
link |
01:38:12.140
and today neuroendocrinology with me.
link |
01:38:15.160
And as always, thank you for your interest in science.
link |
01:38:17.800
I'll see you next time.