Essentials: How Hormones Shape Sexual Development

**Andrew Huberman** (0:00)
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 2X chromosomes and the traditional language around that is that person is female, right? 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 2X chromosomes plus a Y chromosome. There are also cases where it's XYY, where there are 2Y 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 2X 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 Mullerian ducts. 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 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. And for those of you that are not pregnant, things to avoid if you're thinking about eventually having children, and that is not to drive development in one direction or another, but there are examples where there are some deleterious things in our environment that can actually negatively impact what we call sexual development overall, regardless of chromosomal background. 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. This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more. They've also recently added tests for toxins, such as BPA exposure from harmful plastics and tests for PFAS or forever chemicals. Function not only provides testing of over 100 biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas. For example, in one of my first tests with Function, I learned that I had elevated levels of mercury in my blood. Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption. I'd been eating a lot of tuna while also making an effort to eat more leafy greens and supplementing with NAC, N-acetylcysteine, both of which can support glutathione production and detoxification. And I should say by taking a second Function test, that approach worked. Comprehensive blood testing is vitally important. There's so many things related to your mental and physical health that can only be detected in a blood test. The problem is blood testing has always been very expensive and complicated. In contrast, I've been super impressed by Function's simplicity and at the level of cost. It is very affordable. 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/huberman.