In this Huberman Lab Essentials episode, I explain the crucial role hormones play in shaping the sexual development of both the brain and body. I discuss how biological masculinization and feminization depend on factors such as genetics, hormone ratios, and receptor availability. I also explore how hormones like testosterone, estrogen, and other steroid hormones influence sexual characteristics and brain development. Additionally, I examine the impact of environmental factors—such as herbicides like atrazine, cannabis, alcohol, and even cell phones—on hormone function and reproductive health. Huberman Lab Essentials are short episodes (approximately 30 minutes) focused on key science and protocol takeaways from past Huberman Lab episodes. Essentials are released every Thursday, while full-length episodes continue to be released every Monday. Read the full episode show notes, including referenced articles, resources, and people mentioned at hubermanlab.com. This Huberman Lab Essentials episode is from the full-length episode, available here: https://go.hubermanlab.com/PQYuc9i Thank you to our sponsors AG1: https://drinkag1.com/huberman Function: https://functionhealth.com/huberman Our Place: https://fromourplace.com/huberman BetterHelp: https://betterhelp.com/huberman Timestamps 00:00:00 Huberman Lab Essentials; Hormones, Sexual Development 00:01:25 Chromosomal Sex, Gonadal Sex, Hormonal Sex, Morphology 00:06:08 Sponsor: Function 00:07:56 Steroid Hormones, Sexual Characteristics 00:10:59 Primary & Secondary Sexual Characteristics, Dihydrotestosterone (DHT), Kisspeptin 00:15:12 Masculinization of Brain, Estrogen 00:16:29 Sponsors: Our Place, BetterHelp 00:19:15 Herbicides, Atrazine, Hormone Effects, Sperm Counts 00:25:04 Female Sexual Development, Androgen Insensitivity Syndrome 00:28:37 Sponsor: AG1 00:29:41 Cannabis & Aromatase Activity, Gynecomastia; Alcohol & Estrogen Activity 00:32:34 Cell Phones & Gonads 00:35:24 Beard & Hair Growth, DHT 00:38:42 Hyenas, Hormones, Androstenedione; Plants 00:43:44 Recap & Key Takeaways Disclaimer & Disclosures
Chapter 1: What are hormones and how do they function?
Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. This podcast is separate from my teaching and research roles at Stanford.
Today, we're going to explore hormones, what they are, how they work, what leads to masculinization or feminization of the brain and body. What we're trying to do today is really get to the biology, the physiology, the endocrinology, and the behavior.
Hormones by definition are a substance, a chemical that's released in one area of the body, typically from something we call a gland, although they can also be released from neurons, but they're released often from glands that travel and have effects both on that gland, but also on other organs and tissues in the body.
And that differentiates hormones from things like neurotransmitters, which tend to act more locally. Examples of tissues that produce hormones would be the thyroid, the testes, the ovaries, et cetera.
And then of course there are areas of the brain like the hypothalamus and the pituitary, which are closely related to one another and release hormones that cause the release of yet other hormones out in the body. So let's start with development, sperm meets egg. Everything that happens before that is a topic of the next episode. But sperm meets egg. This is mammalian reproduction.
And that egg starts to duplicate. It starts to make more of itself. It makes more cells. And eventually some of those cells become skin. Some of those cells become brain. Some of those cells become muscle. Some of those cells become fingers. All the stuff that makes up the brain and body plan.
In addition, there are hormones that come both from the mother and from the developing baby, the developing fetus, that impact whether or not the brain will be what they call organized masculine or organized feminine.
And as I say this, I want you to try and discard with the cultural connotations or your psychological connotations of what masculinization and feminization are, because we're only centering on the biology. So typically people have either two X chromosomes And the traditional language around that is that person is female, right?
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Chapter 2: How do chromosomes influence sexual development?
Or an X chromosome and a Y chromosome, and that person will become male. Now, it's not always the case. There are cases where it's XXY, where there are two X chromosomes plus a Y chromosome. There are also cases where it's XYY, where there are two Y chromosomes. And these have important biological and psychological impacts.
So the first thing we need to establish is that there is something called chromosomal sex. Whether or not there are two X chromosomes or an X and Y chromosome is what we call chromosomal sex. But the next stage of separating out the sexes is what we call gonadal sex. Typically, not always, but typically, if somebody has testes for their gonads, we think of them as male.
And if somebody has ovaries, we think of them as female. Although that's not always the case either, but let's just explore the transition from chromosomal sex to gonadal sex, because it's a fascinating one that we all went through in some form or another. So this XY that we typically think of as promoting masculinization of the fetus
We say that because on the Y chromosome, there are genes and those genes have particular functions that suppress female reproductive organs. So on the Y chromosome, there's a gene which encodes for something called Mullerian inhibiting hormone.
So there's actually a hormone that's programmed by the Y chromosome that inhibits the formation of Mullerian ducts, which are an important part of the female reproductive apparatus. That's critical because already we're seeing the transition between chromosome Y chromosome and gonad. And other genes on the Y chromosome promote the formation of testes.
So there are genes like the SRY gene and other genes that promote the formation of testes while they also inhibit the formation of the malaria So the transition from chromosomal sex to gonadal sex is a very important distinction. It's kind of a fork in the road that happens very early in development while fetuses are still in the embryo.
So we have to distinguish between chromosomal sex, gonadal sex, and then there's what we call hormonal sex, which is the effects of the steroid hormones, estrogen and testosterone and their derivatives on what we call morphological sex or the shape of the baby and the human and the genitalia and the jaw and all these other things. And so it actually is quite complicated.
So, you know, it's a long distance from chromosomes to gender identity and gender identity has a lot of social influences and roles. This is an area that right now is very dynamic and in the discussion out there, as you know, but just getting from chromosomal sex to what we would call gonadal sex and hormonal sex and morphological sex involves a number of steps.
So today we're going to talk about those steps. And there's some fascinating things that do indeed relate to tools, do indeed relate to some important behavioral choices, important choices about things to avoid while pregnant,
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Chapter 3: What is the role of dihydrotestosterone in sexual development?
So let's get started with that. I'd like to take a quick break and acknowledge one of our sponsors, Function. Last year, I became a Function member after searching for the most comprehensive approach to lab testing. Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health.
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As a consequence, I decided to join their scientific advisory board and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, you can go to functionhealth.com slash Huberman. Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman podcast listeners.
Again, that's functionhealth.com slash Huberman to get early access to Function. Let's talk a little bit more about what hormones do. Hormones generally have two categories of effects. They can either be very fast or they can be very slow. There are hormones like cortisol and adrenaline, which act very fast.
And then there are hormones like testosterone and estrogen, which we refer to as the sex steroid hormones. These molecules, for those of you that are interested, are what are called lipophilic, which just means that they like fatty stuff. They can actually pass through fatty membranes.
And because the outside of cells, as well as what's called the nuclear envelope, where all the DNA contents and stuff are stuffed inside, are made of lipid, of fat, these steroid hormones can actually travel into cells and then interact with the DNA of cells in order to control gene expression.
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Chapter 4: How does estrogen contribute to brain masculinization?
So in puberty, testosterone leads to further growth and development of the penis, as well as the accumulation of, or growth of pubic hair, deepening of the voice, all the secondary sexual characteristics. There's a very interesting phenomenon that was published in the journal Science in the 1970s, for which now there's a wealth of scientific data.
And this relates to a genetic mutation where 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone, doesn't exist. It's mutated. And this actually was first identified in the Dominican Republic. What happens is, baby is born, if you were to look at that baby, it would look female. There would be very little or no external penis.
And what was observed is that from time to time, that baby, after being raised as a girl, would, around the age of 11 or 12 or 13,
would start to sprout a penis there's actually a name for this it's called huevidosis which the translation is more or less penis at 12. and as strange as this might sound it makes sense if you understand the underlying mutation what happens in these children these huevidosis is that the child is born it has testes which are not descended so up in the body
Chapter 5: What are the environmental factors affecting hormone function?
They weren't able to convert testosterone to dihydrotestosterone because they lack this enzyme 5-alpha reductase. As a consequence, the primary sexual characteristic of external male genitalia, penis, doesn't develop.
And then what happens is the baby grows up and then testosterone starts getting secreted from the testes because caspeptin in the brain signals through gonadotropin and luteinizing hormone travels down to the testes. The testes start churning out testosterone and there's a secondary growth of the penis. And all of a sudden there's a penis. And the point here is
that dihydrotestosterone, not testosterone, is responsible for this primary growth of the penis, and that testosterone later is involved in the secondary sexual characteristics, deepening in the voice, et cetera. Now, this is where the information gets even more interesting and applies to essentially everybody.
You might think that testosterone, because it masculinizes the body in the secondary sexual characteristic way, and because dihydrotestosterone, another androgen, masculinizes the primary sexual characteristics, the growth of the penis early on, that testosterone must masculinize the brain. But the masculinization of the brain is not accomplished by testosterone. It is accomplished by estrogen.
testosterone can be converted into estrogen by an enzyme called aromatase there are neurons in the brain that make aromatase and convert testosterone into estrogen in other words it's estrogen that masculinizes the x y individual that masculinizes the brain and this has profound effects on all sorts of things on behavior on outlook in the world, et cetera.
But I think most people don't realize that it's estrogen that comes from testosterone that masculinizes the male brain, the XY brain, not testosterone nor dihydrotestosterone. I'd like to take a quick break and acknowledge one of our sponsors, Our Place. Our Place makes my favorite pots, pans, and other cookware.
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