How Hormones Shape Sexual Development | Huberman Lab Essentials
Date: 2025-02-13 | Duration: 00:39:22
Transcript
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, and what leads to masculinization or feminization of the brain and body.
0:30 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. 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
1:00 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, etc. 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
1:30 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. 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,
2:00 that impact whether or not the brain will be what they call organized masculine or organized feminine. As I say this, I want you to try and discard the cultural connotations or your psychological connotations of what masculinization and feminization are, because we’re only centering on the biology. Typically, people have either two X chromosomes—and the traditional language around that is that person is female—
2:30 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
3:00 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
3:30 sex, because it’s a fascinating one that we all went through in some form or another. 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. On the Y chromosome, there’s a gene which encodes for something called Müllerian inhibiting hormone.
4:00 So there’s actually a hormone that’s programmed by the Y chromosome that inhibits the formation of Müllerian ducts, which are an important part of the female reproductive apparatus. That’s critical because already we’re seeing the transition between Y chromosome and gonad. Other genes on the Y chromosome promote the formation of testes. There are genes like the SRY gene and other genes that promote the
4:30 formation of testes while they also inhibit the formation of the Müllerian ducts. 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. 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
5:00 testosterone and their derivatives on what we call morphological sex, or the shape of the baby in the human, and the genitalia and the jaw and all these other things. It actually is quite complicated. 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, hormonal sex, and morphological sex
5:30 involves a number of steps. 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. 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
6:00 actually negatively impact what we call sexual development overall, regardless of chromosomal background. Let’s get started with that. 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
6:30 lipophilic, which just means that they like fatty stuff. They can actually pass through fatty membranes. Because the outside of cells, as well as the nuclear envelope where all the DNA contents are stuffed inside, are made of lipid, these steroid hormones can actually travel into cells and then interact with the DNA of cells in order to control gene expression. They can change the sorts of things that cells will become and they can change the way that cells function in a long-term way.
7:00 That’s actually how the presence of these genes like SRY and Müllerian inhibiting hormone lead to reductions or elimination of things like the Müllerian ducts and promote instead what’s called in males the Wolffian ducts, or promote the development of testes rather than ovaries. All you need to know is that hormones have short-term and long-term effects, and the long-term effects are actually related to their effects on genes and how those genes are expressed or repressed
7:30 in order to prevent them from having particular proteins made. These hormones, these steroid hormones, are exceedingly powerful. If we’re going to have a discussion about masculinization or feminization, you also need to think about the counterpart. It’s not just about masculinizing the body or feminizing the body and brain; it’s also about demasculinizing the brain in many cases as a normal biological function of typically XX females and
8:00 defeminization—the suppression of certain pathways that are related to feminization of the body and brain. I’ve just thrown a lot of biology at you, but this is where it all starts to get incredibly surprising. You would think that it’s straightforward, right? You have a Y chromosome, you suppress the female reproductive pathway like the Müllerian ducts, you promote the development of testes, and then testes
8:30 make testosterone, and then it organizes the brain male and it wants to do male-like things, and then in females you get estrogen and it wants to do female-like things—and air quotes here for all of this. It turns out that isn’t how it works at all. Here’s where it’s interesting: we have to understand that there are effects of these hormones, testosterone and estrogen, on what are called primary sexual characteristics, which are the ones that you’re born with, and secondary sexual characteristics, which
9:00 are the ones that show up in puberty. These are happening in the brain and body and spinal cord, and so I’m going to disentangle all this for you by giving you some examples. First, let’s talk about the development of primary sexual characteristics, the ones that show up at birth. One of the more dramatic examples of this comes from the role of testosterone in creating the external genitalia. It turns out that it’s not testosterone that’s responsible for
9:30 the development of the penis in a baby that has an X chromosome and a Y chromosome. It’s a different androgen. Androgen is just a category of hormones that includes testosterone, but testosterone is converted in the fetus to something called dihydrotestosterone, and that’s accomplished through an enzyme called 5-alpha reductase. Dihydrotestosterone is what we would call the dominant androgen in males. It’s
10:00 responsible for aggression, it’s responsible for a lot of muscular strength, it’s involved in beard growth and male pattern baldness—we’re going to talk about all of that—but dihydrotestosterone has powerful effects in determining the genitalia while the baby is still in the embryo. Testosterone is made, and that testosterone gets converted by this enzyme 5-alpha reductase in a little structure called the tubercle. That tubercle will
10:30 eventually become the penis. So you say, “Okay, straightforward. This testosterone’s converted to dihydrotestosterone, and then if there’s dihydrotestosterone, it controls penis growth.” And indeed, that’s the case. So that’s a primary sexual characteristic. That baby will then grow up and later, during puberty, there will be the release of a molecule—I talked about this last episode—called kisspeptin (K-I-S-S-P-E-P-T-I-N). Kisspeptin will cause the release of
11:00 some other hormones: gonadotropin-releasing hormone and luteinizing hormone will stimulate the testes to make testosterone. So in puberty, testosterone leads to further growth and development of the penis as well as the accumulation 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
11:30 reductase, the enzyme that converts testosterone to dihydrotestosterone, doesn’t exist; it’s mutated. This actually was first identified in the Dominican Republic. What happens is a baby is born, and if you were to look at that baby, it would look female. There would be very little or no external penis. What was observed is that from time to time, that baby, after being raised as a girl,
12:00 would around the age of 11 or 12 or 13 start to sprout a penis. There’s actually a name for this: it’s called guevedoces, which the translation is more or less “penis at 12.” As strange as this might sound, it makes sense if you understand the underlying mutation. What happens in these children, these guevedoces, is that the child is born with testes which are not descended—they are up in
12:30 the body. They weren’t able to convert because they lack this enzyme 5-alpha reductase. As a consequence, the primary sexual characteristic of external male genitalia, the penis, doesn’t develop. And then what happens is the baby grows up, and then testosterone starts getting secreted from the testes because kisspeptin in the brain signals through gonadotropin and luteinizing hormone travels down to the testes. The testes
13:00 start churning out testosterone, and there’s a secondary growth of the penis, and all of a sudden there’s a penis. 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 of the voice, etc. Now, this is where the information gets even more interesting and applies to essentially everybody. You might think that
13:30 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
14:00 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 XY individual, that masculinizes the brain, and this has profound effects on all sorts of things: on behavior, on outlook in the world, etc. But I think
14:30 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 just want to mention some tools. You might be asking yourself how could tools possibly come up at this stage of the conversation where we’re talking about sexual development and we’re talking about the differentiation of tissues in the body. Well, this is true both for children and parents and adults. I want to emphasize that there are
15:00 things that are environmental and there are things that people use that actually can impact hormone levels and can impact sexual development in fairly profound ways. I want to be very clear: this is not me pulling from some rare journal I’ve never heard of; this is pulling from textbooks. In particular, today I’m guiding a lot of the conversation on work on behavioral endocrinology, which is a book by Randy Nelson and
15:30 Lance Kriegsfeld, true experts in the field. I’m going to talk about some of the work from Tyrone Hayes at UC Berkeley about environmental toxins and their impacts on some of these things like testosterone and estrogen. I’m going to touch into them; I’m going to give some anecdotal evidence that’s grounded in studies which we will provide in the caption or that I’ll reference here. Again, I’m just going to highlight: when one starts talking about environmental factors and how they’re poisoning us or disrupting growth or fertility rates, it can start
16:00 to sound a little bit crazy, except when you start to actually look at some of the real data—data from quality research labs funded by the federal government, not from companies or other sources that are really aimed at understanding what the underlying biology is. For that, we should all be grateful to Tyrone Hayes at UC Berkeley. I remember way back when I was a graduate student in the late ’90s at UC Berkeley, and I remember him—he was studying frogs. He was talking about
16:30 developmental defects in these frogs that live in different waters around California, but also elsewhere. He identified a substance which is present in a lot of waterways throughout this country and other countries—so the US and beyond, certainly not just restricted to California—which is atrazine (A-T-R-A-Z-I-N-E). Again, this is the stuff of textbooks, and it causes severe testicular malformations. Atrazine exposure is serious.
17:00 What’s interesting is if you look at the data, what you find is that at sites in Western and Midwestern sections of the United States, 10 to 92% of male frogs—these were frogs, mind you—had testicular abnormalities. The most severe testicular malformations were in the testes rather than in the sperm; it’s actually the organ itself, the gonad itself. It’s very well known now that
17:30 atrazine is in many herbicides. Whereas I would say in the ’80s and ’90s the discussion around herbicides and their negative effects was considered kind of hippie-dippy stuff or the stuff you hear about at your local community markets and these kind of New Agey communities, now there’s very solid data from federally funded labs at major universities that have been peer-reviewed and published in excellent journals showing that indeed many of these herbicides can have negative
18:00 effects, primarily by impacting the ratios of these hormones in either the mothers or in the testes, altering the testes of the fathers, or direct effects on developing young animals and potentially humans. So you ask, “Well, what about humans? Frogs are wonderful, but what about humans?” Here are the data on what’s happening—and this isn’t all going to be scary stuff; we’re also going to talk
18:30 about tools to ameliorate and offset some of these effects depending on your needs. Across human populations, sperm counts are indeed declining. In 1940, the average density of human sperm was 113 million per milliliter of semen. That’s how it’s measured: how many sperm per milliliter of semen. In 1990, this figure had dropped to 66. It went from 113 million per milliliter to 66 million per
19:00 milliliter in the United States and Western Europe, so it’s not just a US thing. Researchers also estimated that the volume of semen produced by men has dropped 20% in that time, reducing sperm count per ejaculation even further. Between 1981 and 1991, the ratio of normal spermatogenesis has decreased from 56.4% to 26.9%. So there’s a lot that’s happening, primarily because of these herbicides that are in widespread use, to
19:30 reduce sperm counts. These are going to have profound effects not just on sperm counts, but on development—sexual development at the level of the gonads and the brain. Because you need testosterone to get you dihydrotestosterone for primary sexual characteristics, you need estrogen that’s come from testosterone to masculinize the brain. And of course, we’re not just focusing on sperm and testosterone; you of course also know that many of these herbicides are disrupting estrogens in a
20:00 similar way, which might explain why puberty is happening so much earlier in young girls these days. There are a lot of things that are happening. Now, does this mean that you have to run around and neurotically avoid anything that includes things like atrazine and should you be avoiding all kinds of herbicides? I don’t know; that’s up to you. But it does seem that these have pretty marked effects in both the animal studies and in the human studies. Let’s talk about female
20:30 sexual development. As always, what we’ll do is we’ll talk about the normal biology, then we’ll talk a little bit about a kind of extraordinary or unusual set of cases, but we’ll talk about them because they illustrate an important principle about how things work under typical circumstances. There is a mutation called androgen insensitivity syndrome, and understanding how androgen
21:00 insensitivity syndrome works can help you really understand how hormones impact sexual development. Here’s how it works: there are individuals who are XY, so they have a Y chromosome, that are born, that make testosterone, they have testes, and they don’t have Müllerian ducts because on the Y chromosome is this Müllerian inhibiting hormone. However, these individuals look completely female, and in general, they
21:30 report feeling like girls when they’re young and women when they’re older. But there’s something unusual that’s happening in these individuals because they have an XY chromosomal type and not XX. What’s happening? Well, what’s happening is the testes are making testosterone, but the receptor for testosterone is mutated. Therefore, the testes never descend. They don’t have ovaries; they have testes, but
22:00 the testes are internal. Typically, these individuals find out that they are actually XY chromosomes—so their chromosomal sex is male, if you will, and their gonadal sex is male—but the gonads, the testes, are inside the body. They don’t actually develop a scrotum, they don’t make ovaries, and when they don’t menstruate around the time of puberty, that’s a sign that something is different. They never menstruate around puberty, and if they look into
22:30 this deeply enough, what you find is that they are actually XY. They make testosterone, but their body can’t make use of the testosterone because they don’t have the receptors. The receptors are vitally important for most all of the secondary sexual characteristics that we talked about: body hair, penis growth during puberty, etc. Again, we’re talking about this in order to illustrate the principle that in order to have its effects, a hormone doesn’t just have to be present; that hormone actually has to be able to bind
23:00 its receptor and take action on the target cells. Perhaps the simplest way to understand how estrogen and testosterone impact masculinization or feminization of the brain and behavior is from a statement—it’s actually the closing sentence of an abstract that my colleague Nirao Shah at Stanford School of Medicine published—which is that estrogen (again, it’s estrogen that is aromatized from testosterone by
23:30 aromatase) sets up the masculine repertoire of sexual and, in animals and in humans, territorial behaviors. It sets up the circuitry in the brain; estrogen does that. Estrogen sets up the masculine circuitry in the brain, and testosterone is then what controls the display of those behaviors later in life. I find that incredibly interesting. You would think it was just testosterone did one thing and estrogen did another, but it turns out that nature is far more
24:00 interesting than that. Okay, so what are some things that impact sexual development early in life and later in life? Let’s talk about cannabis; let’s talk about alcohol. First of all, cannabis, marijuana, THC: there are many studies that point to the fact that THC and other things in cannabis promote significant increases in aromatase
24:30 activity. Pot smokers aren’t going to like this, especially male pot smokers aren’t going to like this, but it’s the reality. Here’s the deal: cannabis—and it’s not clear if it’s THC itself or other elements in the marijuana plant—promotes aromatase activity. This has been observed anecdotally where pot smokers have a higher incidence of developing something I mentioned before, gynecomastia: breast bud development or
25:00 full-blown breast development in males. Earlier I said that estrogen is what masculinizes the male brain in utero; that’s true. But the way that cannabis seems to work, at least from the studies I was able to identify, is that it promotes circulating estrogen in the body and therefore can counteract some of the masculinizing effects of things like testosterone and dihydrotestosterone on primary and secondary sexual characteristics. I mention this because
25:30 nowadays marijuana use is far more widespread, and certainly during puberty it can have profound effects on these hormonal systems. We’ll do another episode that goes really deep into this, but yes, cannabis promotes estrogenic activity by increasing aromatase. Most everyone can appreciate that drinking during pregnancy is not good for the developing fetus. Fetal alcohol syndrome is a well-established negative outcome of pregnancy, and it’s
26:00 something where there are cognitive effects that are really bad, there’s actually physical malformation, etc. Drinking during pregnancy: not good. Probably drinking during puberty: not good either, because alcohol—in particular certain things like beer, but other grain alcohols—can increase estrogenic activity. This isn’t just about protecting young boys from estrogenic activity; it’s also
26:30 protecting girls from excessive or even hypoestrogenic effects of alcohol in puberty. Many teenagers drink, college students drink, and it’s important to point out that puberty doesn’t start on one day and end on another day. Puberty has a beginning, a middle, and an end, but development is really our entire lifespan. Okay, so we talked about cannabis, we talked about alcohol. Let’s talk about cell phones.
27:00 First of all, I use a cell phone. I use it very often, and I do not think they are evil devices. I think that they require some discipline in order to make sure that it does not become a negative force in one’s life. I personally restrict the number of hours that I’m on the phone and, in particular, on social media. But what about the cell phone itself? When I was a junior professor—pre-tenure, early professor—I taught this class on neural
27:30 circuits and health and disease, and one of the students asked me, “Are cell phones safe for the brain?” All the data point to the fact that they were, or at least there were no data showing that it wasn’t. I still don’t have the answer on that, frankly. I’m not personally aware of any evidence in quality peer-reviewed studies showing that cell phones are bad for the brain, or that holding the phone to the ear is bad, or that Bluetooth is bad, or any of that. I’m just not aware of any quality studies. However, I was very interested in
28:00 a particular study that was published back in 2013 on rats. It basically took a cell phone and put it under a cage of rats and looked at testicular and ovarian development in rats and saw minor but still statistically significant defects in ovarian and testicular development. Since then, and now returning to the literature, I’ve seen an absolute
28:30 explosion of studies, some of which are in quality journals, some of which are in what I would call not Blue Ribbon journals, identifying defects in testicular and/or ovarian development by mere exposure to cell phone emitted waves. Let’s just call that—we don’t know what they are. This sounds almost crazy, right? Anytime somebody starts talking about EMF and things like that, you kind of worry, like, is this person okay? But the
29:00 literature are pointing in a direction where chronic exposure of the gonads to cell phones could be creating serious issues in terms of the health at the cell level and then in terms of the output. The output for the testes would be sperm production—swimming speed in sperm is an important feature of sperm health. In the ovaries, it would be estrogenic output, how regular the cycles are. I think that it’s fair to
29:30 say, based on the literature, that there are effects of cell phone emitted waves on gonadal development. The question is: what is the proximity of the cell phone to the gonads? You have to take these sorts of studies with a grain of salt. There’re some interesting effects of hormones that actually you can observe on the outside of people that tell you something about not just their level of hormones, but also about their underlying genetics, and these relate to beard growth and baldness. It’s fascinating.
30:00 The molecule, the hormone dihydrotestosterone made from testosterone, is the hormone primarily responsible for facial hair, for beard growth. As well, it’s the molecule, the hormone primarily responsible for lack of hair on the head, for hair loss. Not incidentally, the drugs that are designed to prevent hair loss are 5-alpha
30:30 reductase inhibitors. Remember 5-alpha reductase from the guevedoces? Well, the people that discovered the guevedoces went on to do a lot of research on the underlying biochemistry of this really interesting molecule, dihydrotestosterone. They identified 5-alpha reductase, and 5-alpha reductase inhibitors are the basis of most of the anti-hair loss treatments that are out there. There are some interesting things here. First of all, the side effect profiles of those treatments for hair
31:00 loss are quite severe in many individuals. Remember, DHT is the primary androgen for libido, for strength and connective tissue repair, for aggression—even if that aggression, of course, is held in check—but just sort of ambition and aggression is related to dopamine but within the testosterone pathway. Less so pure testosterone, although pure testosterone has its effects, but DHT is, at least in primate
31:30 species including humans, the dominant androgen for most of those sorts of effects. If you look at somebody, everyone can predict whether or not they’re going to go bald based on looking at their—we’re always taught our mother’s father. So if your mother’s father was bald, there’s a higher probability that you’re going to go bald. The pattern of DHT receptors on the scalp will dictate whether or not you’re going to go bald everywhere or just in the front or so-called crown-type baldness.
32:00 The density of the beard tells you about the density of DHT receptors. This varies by genetic background. There are areas of the world where all the men seem to have the same pattern of baldness, like a strip of baldness down the center with hair still on the sides and full beards. That’s because these patterns of DHT receptors are genetically determined. Elsewhere, testosterone levels can still be very high, DHT levels in the blood can be very high, and yet people will have very
32:30 light beards or no beards, and that’s because they don’t have a lot of DHT receptors in the face. There are a lot of effects of DHT that you can just see in male phenotypes, and it’s interesting that these hair loss drugs are directly aimed at preventing the conversion of testosterone into dihydrotestosterone. That’s why they to some extent prevent hair loss, but also to some extent have a bunch of side effects
33:00 that are associated with low DHT. I want to tell you a story about hyenas and clitorises the size of penises. When I was a graduate student at UC Berkeley, we had a professor in our department, a phenomenal scientist named Steve Glickman. Steve Glickman had a colony of hyenas, spotted hyenas, that lived within caged enclosures in Tilden Park behind the UC Berkeley campus. The hyenas are no longer there. Hyenas exhibit an incredible feature to their body, their hormones, and their social structure.
33:30 Hyenas, unlike many species, have a situation with their genitalia where the male penis is actually smaller than the female clitoris. I should say that the male penis itself, having seen a fair number of hyena penises, is not particularly small, which means that the hyena clitorises are extremely large. This was well known for some time. It turns out that in these spotted hyenas, the females are dominant. After a kill, the females will eat, then their young will eat, and then the male hyenas will eat as well.
34:00 When the female hyena gives birth, she gives birth not through the vaginal canal that we’re accustomed to seeing, but through a very enlarged clitoris-like phallus—although it’s not a phallus, it’s a clitoris—and it literally splits open. Many fetuses die during the course of hyena development and birth. The baby hyena actually comes through the tissue and it’s a very
34:30 traumatic birth. It was a mystery as to how the female hyenas have this—we’ll call it masculinization, but it’s really an androgenization of the periphery of the genitalia. It turns out, through a lot of careful research done by Steve Glickman, Christine Drea, and others, that it’s androstenedione—what is essentially a prohormone to testosterone. It’s androstenedione at very
35:00 high levels that’s produced in female hyenas that creates this enlargement of their genitalia. If you want to read up on androstenedione, androstenedione is made into testosterone through this enzyme 17-beta-hydroxysteroid dehydrogenase. It’s a complicated pathway to pronounce; it’s a fairly straightforward pathway biochemically. You may recall during the ’90s and 2000s
35:30 there were a lot of performance-enhancing drug scandals, in particular in Major League Baseball. It was purported, although I don’t know that it was ever verified, that the major performance-enhancing drug of abuse at that time—in particular players whose names we won’t mention, but you can Google it if you want to find out—was androstenedione. The last little anecdote about this, which is also published in the scientific literature, which is weird but I do find interesting—
36:00 hormones are so fascinating, they’re just incredible to me—is going back to the marijuana plant. The marijuana plant has these estrogenic properties, and I asked a plant biologist whether or not this was unusual. This plant biologist told me, “Oh yeah, there are plants that make what is essentially the equivalent of testosterone, like pine pollen—it looks a lot like testosterone—and there are other plants that make what is essentially estrogen.”
36:30 I said, “Well, why would they do that?” He said that one of the reasons why some plants have evolved this capacity to increase estrogen levels in animals that consume them—I’m guessing that animals aren’t smoking marijuana, although I don’t know; send me the paper if you’ve heard of this—is that plants have figured out ways, they’ve adapted ways to push back on populations of rodents and
37:00 other species of animals that eat them. Plants are engaged in a kind of plant-to-animal warfare where they increase the estrogen of the males in that population to lower the sperm counts, to keep those populations clamped at certain levels so that those plants can continue to flourish. I find this just fascinating. Hormones aren’t just impacting tissue growth and development within the individual and between the mother—remember the placenta is an endocrine organ—and the offspring,
37:30 but plants and animals are in this communication. It’s a fascinating area of biology. As you’ve noticed today, none of this deals with the current controversies around gender and how many genders and sex, etc. That’s a separate conversation that is, by definition, grounded in the kind of concepts we’ve been talking about today and needs to take place taking into consideration all of the aspects of sex and the effects of hormones both on the body and on the brain. We didn’t talk a lot about spinal cord,
38:00 but we will in the next episode. We can just say on the brain and the periphery: early effects, late effects, acute effects—meaning effects that are very fast, of levels of hormones going up or down, something that absolutely happens across the menstrual cycle—as well as long-term effects, like the effects of these hormones on gene expression. Today, as always, we weren’t able to cover all things related to sex and
38:30 hormones and sexual differentiation or development—there’s no way we could—but we have covered a lot of material. Once again, I want to thank you for embarking on this journey through neuroscience and, today, neuroendocrinology with me. As always, thank you for your interest in science.