Chapter 12: Sex: Evolutionary, Hormonal & Neural Bases

Welcome to Last Minute Lecture.

This free chapter overview is designed to help students review and understand key concepts.

These summaries supplement not replaced the original textbook and may not be redistributed or resold.

For complete coverage, always consult the official text.

I want to start today with a story that it honestly reads like a psychological thriller, but it's a real medical case study.

It goes back a few decades, but you still see the implications being debated in neurobiology classrooms today.

It centers on a child who's referred to in the literature as Bella.

It's a profound story.

It really is.

It's one of those rare cases where a single medical crisis just forces us to confront the very definition of identity.

It really sets the stage perfectly for everything we're going to talk about today, the whole biological versus social aspect of who we are.

So let's set the scene.

Bella is born, and immediately the delivery room goes quiet.

There's catastrophic developmental defect.

It's called colical extrophy.

It's incredibly rare.

Incredibly rare, like one in 400 ,000 births.

And basically, the abdominal wall just hasn't closed properly during development.

The intestines are exposed.

The pelvis is malformed.

The bladder is split open.

It's life -threatening.

Oh, absolutely.

I mean, it requires immediate, really complex surgery just to ensure the child survives those first few days.

Right.

But once that immediate threat to life is managed, the parents and the surgeons are left with this secondary, just agonizing dilemma.

You see, genetically, this child was male.

XY chromosomes.

XY chromosomes.

Fully formed tests.

But because of how severe the defect was, the penis was completely absent.

And this is where you have to understand the context of the era, the thinking at the time.

Exactly.

The prevailing psychological theory was that gender was largely a social construct.

The idea was that humans are

psychosexually neutral.

That was the term.

Yeah, psychosexually neutral.

And that nurture could override nature if you just started early enough.

It was often called the optimal gender of rearing model.

So the medical team looked at this pragmatically.

They reasoned, okay, is it better to raise this child as a boy who has no penis, facing a lifetime of difficult surgeries and likely psychological trauma about his virility?

Or is it better to remove the testes, surgically fashion genitalia that appear female, and raise the child as a girl?

It's an impossible choice.

An impossible choice, but they chose the latter.

They removed the tests.

They assigned the child the female gender.

Bella was raised as a daughter.

Wore dresses, played with dolls.

The whole thing.

Everyone, her parents, her teachers, her friends, treated her as a girl.

She didn't know any different.

The secret was absolute.

So this is the ultimate test, right?

This is the ultimate test of the nurture hypothesis.

If gender is just learned, Bella should have grown up to be a perfectly happy, well -adjusted girl.

But that is not what happened.

By the time Bella was 12, the cracks were already showing.

She was described as a tomboy, which, okay, that's common enough.

That doesn't mean anything on its own.

But she also reported feeling profoundly out of place.

She didn't fit in with the other girls.

She felt different in a way she couldn't really articulate.

And then puberty hits.

Some puberty hits.

At age 12, her parents sit her down.

They essentially say, we need to tell you the truth about your birth.

Just imagine that moment.

You're 12 years old, you're on the verge of adolescence, and your parents tell you that your entire identity has been a well -intentioned fabrication.

You'd expect denial, right?

A total breakdown.

But Bella's reaction was the opposite.

She reportedly said, I knew it was true.

Wow.

That's the pivotal data point right there.

I mean, despite 12 years of intense social conditioning, despite every single external cue telling her she was female, something internal, something written in the hardware, just rejected it.

She said, even if it had been another person that told me, I would have believed them because it made sense to me.

And almost immediately, Bella becomes Benjamin.

Instantly.

He cuts his hair, puts on boys' clothes, and goes to school a week later as a male.

He transitioned on a dime.

In that case study, it perfectly frames the central tension of our deep dive today.

We're looking at Chapter 12 of Behavioral Neuroscience by Breedlovin Watson, which covers sex, evolutionary, hormonal, and neural bases.

The story of Benjamin forces us to ask, how much of our sexual identity, our behavior, our orientation is written into our wiring before we're even born?

Is it nature or is it nurture?

And his story suggests that the wiring, that prenatal organization of the brain, is incredibly powerful.

Maybe even more so than a decade of socialization.

It's a fascinating if, yeah, a somewhat heavy place to start.

But our mission today is to take that question and really look at the mechanics behind it.

We're going to walk through this chapter methodically.

Right.

We'll start with the behavior itself, from the birds and the bees, literally, and then move into the hormones, the specific neural circuits, and finally that developmental cascade that makes us male or female.

Yeah, we're going to break this down logically.

We'll start with the four stages of reproductive behavior that you see in almost all animals.

Then we'll look at the hormones, the chemical messengers.

Then we get into the actual neural circuitry, the brain's wiring diagram.

And then finally we'll tackle sexual differentiation and the biological roots of sexual orientation.

I have to say, looking at source material, there are some things coming up that really surprised me.

We tend to think of sex as just the act, but biologically, it's this highly staged production.

It is.

It really is.

To reproduce successfully, animals can't just jump to the finish line.

It's a coordinated dance.

And the text defines four very distinct stages, sexual attraction, appetite behavior, copulation, and post -copulatory behavior.

Okay, so let's start with stage one, sexual attraction.

This seems self -explanatory, right?

You have to find someone appealing.

But the biology of what we call appeal is just ruthless.

The text uses the peacock as the classic example.

You can see it in figure 12 .1.

The peacock is the poster child for sexual selection.

I mean, you have a male bird dragging around a tail that is heavy, it's metabolically expensive to grow, and it makes him highly visible to predators like tigers.

It's a liability.

It is.

From a pure survival standpoint, just natural selection, it's a disaster.

It's a handicap.

So why does evolution keep it?

I mean, why hasn't nature selected against this giant clumsy tail?

Because it acts as an honest signal of genetic fitness.

It's what biologists call the handicap principle.

The handicap principle.

Right.

The logic is if a male can survive despite carrying around this giant heavy neon sign on his back, he must have incredible genes.

He must be strong, fast, disease -free.

Yeah.

The female, the P hen, chooses him not because the tail is pretty in some aesthetic sense, but because the tail proves he's a survivor.

It's a high -stakes gamble.

It's like saying, I'm so tough I can fight with one hand tied behind my back.

Exactly.

Now, attraction leads to pair bonds, and this is where we have to talk about voles.

We've mentioned voles before in other deep dives about oxytocin, but this chapter makes a really crucial distinction between social monogamy and sexual monogamy.

And this is a vital distinction.

It often gets lost in pop science.

We look at prairie voles, and we see them living together, nesting together, raising pups together, and we call them monogamous.

Right.

But that's social monogamy.

If you actually do genetic testing on the pups in that nest, you find that the male partner isn't always the father of all of them.

So they cheat.

They engage in what's called extra pair copulation.

In evolutionary terms, it's a hedging strategy.

You get the stability of a partner to help raise the offspring, which increases their survival rate, but you also mix your genes with others to increase diversity.

So true sexual monogamy is actually really rare.

Exceptionally rare in the animal kingdom.

The text also throws a little shade at human attraction.

Apparently we are terrible at reading signals.

We really are.

Studies consistently show this mismatch.

Men tend to overestimate a woman's sexual interest.

They mistake friendliness for attraction.

And conversely, women tend to underestimate a man's sexual interest.

Is there an evolutionary reason for making that kind of error?

Well, the leading theory is something called error management.

For a male, missing a reproductive opportunity is a very high cost genetically.

So it's better to have a false alarm to assume she's interested when she isn't than to miss a chance.

And for a female?

For a female, the cost of mating with a low quality or, you know, a non -investing male is high.

So skepticism is just the safer bet.

That makes sense.

And the text also notes that learned associations play a huge role in humans.

The entire fashion industry, for example, is built on pairing neutral objects like shoes or cars with sexually attractive imagery to create a conditioned response.

Right.

That brings us to this data too.

Appetitive behavior.

So if attraction is spotting someone across the bar, appetitive behavior is walking over and buying them a drink.

It's the maintenance of the interaction.

Exactly.

It's courting.

And there's a term here I really want to highlight because it changes how we view female agency in biology.

Perceptive.

Perceptive.

As opposed to just.

Perceptive.

We often think of the female in the animal kingdom as passive, just waiting to be chosen.

But that's just not true.

A female rat, for example, is perceptive.

She actively encourages the male.

The text describes behavior like ear wiggling.

I tried to picture this, a rat wiggling its ears.

It's a rapid vibration of the ears.

She also does a hopping and darting gait.

She hops away then stops and looks back at him.

She's inducing the male to chase her.

So she's initiating.

She is driving the interaction, setting the pace.

If she doesn't do this, the male often won't even mount.

So she wiggles, he chases.

And that leads to stage three, copulation, the act itself.

And here's where we get into the mechanics of the rat, which are surprisingly bureaucratic.

It's not a simple event, no.

In rats, copulation involves a series of introvisions.

Introvisions.

The male inserts the penis, but then immediately springs back.

He does this multiple times, like seven to nine times before he actually ejaculates.

That seems really inefficient.

If you're a prey animal, you want to get this done and get back to safety.

Why the delay?

But that's the why question we always need to ask.

And it turns out there's a physiological necessity for it.

The female rat's brain needs that specific pattern of repeated mechanical stimulation to trigger the release of hormones,

specifically the hormones to support a pregnancy.

If the male ejaculated on the first try, her body wouldn't be hormonally prepared to accept the sperm or implant the egg.

So his behavior is directly unlocking her physiology.

It's like entering a passcode.

You can't just hit enter.

You have to type in all the numbers in the right order.

Wow.

Precisely.

And speaking of copulation, we have to talk about the Coolidge Effect.

Yes.

Figure 12 .2.

The story of Sooty,

the guinea pig.

This is a legend.

It's a very humorous story, but it illustrates a hard -coded biological principle.

So tell us about Sooty.

Okay.

So Sooty was a male guinea pig, just a household pet.

One night he escapes his cage.

He manages to break into a nearby pen that's housing 24 female guinea pigs.

A target rich environment.

He was missing for two days.

When the owners finally found him, he was asleep in the corner, just absolutely emaciated and exhausted.

But in those two nights, he had sired a 43 offspring.

43.

Sooty was busy.

But the biological principle here is about the refractory period.

Normally after a male mammal mates and ejaculates, he enters a refractory phase, a recovery time, where he cannot or will not mate again.

He's biologically done for a while.

But Sooty didn't stop.

Because of the Coolidge Effect.

The refractory period is drastically shortened or even eliminated if the male is presented with a new partner.

A new partner.

That's the key.

That's the key.

The name comes from an old joke about President Calvin Coolidge.

He and his wife were touring a farm and the first lady saw a rooster mating and asked the farmer,

does he do that more than once a day?

The farmer says dozens of times.

He says, please tell that to the president.

Okay.

So when the president is told, he asks the farmer, same hand every time.

The farmer says, no, sir.

A different one each time.

And Coolidge says, tell that to Mrs.

Coolidge.

It's a classic.

But the biology is serious.

It's a mechanism to maximize genetic spread.

If a new opportunity arises, the system overrides the fatigue.

Correct.

And this ties into the concept of estrus or heat.

In many mammals, females are only receptive at very specific times when they're ovulating.

If they aren't in estrus, they won't mate.

But when they are and you have a male with the Coolidge effect, well, you get sooty.

Okay.

Final stage.

Stage four.

Post -copulatory behavior.

This is what happens after the act.

Grooming, parental care.

But there's a specific phenomenon here called the copulatory lock.

This is something you see in dogs and southern grasshopper mice.

After ejaculation, the penis swells to such a degree, specifically a structure called the bulbous glandus, that it cannot be removed from the female.

You're stuck.

They are physically locked together tail to tail for 10 or 15 minutes.

And the text makes a very specific point to debunk a myth here.

Humans do not get stuck.

Correct.

There was this persistent urban myth started by a medical prank back in 1884,

claiming humans could get stuck in a lock or captivus.

It is anatomically impossible for humans.

We just don't have the erectile structure for it.

So in dogs, what's the point?

It's a strategy to ensure paternity.

Basically preventing another male from mating while the sperm gets a head start.

Okay.

So those are the stages.

But what's driving all this?

What is the ender under the hood?

That brings us to section two.

The mechanics of mating.

We're talking hormones.

Hormones are the key.

But before we get to the hormones, let's just briefly touch on fertilization itself.

Most of what we're discussing is internal fertilization mammals, birds.

But you have fish and amphibians that often use external fertilization, just releasing gametes into the water.

And then there's parthenogenesis.

The virgin birth.

Yes.

Some vertebrates can reproduce asexually.

Turkeys can actually do this occasionally.

Really?

Komodo dragons too.

And there's a species called the Amazon Mollea fish that is entirely female.

They essentially just clone themselves.

It's a fascinating exception to the rule.

But for us mammals, we need hormones and we need to distinguish between how they work in developing bodies versus adult bodies.

In adults, we say hormones have an activational effect.

Right.

They temporarily turn on a behavior.

Like a key in the ignition.

Exactly.

For example, if you castrate a male rat, remove the source of testosterone, he will eventually stop mounting females.

The behavior just disappears.

But if you give him testosterone therapy, the behavior comes back.

The hormone activates the existing circuitry.

But here is where it gets really interesting.

Figure 12 .4 describes the drive experiment.

And this blew my mind because I think most people assume that testosterone operates like a gas pedal.

More hormone equals more drive.

That is the common assumption.

If a man has low libido, he thinks I need more testosterone.

If someone is hypersexual, we assume they have too much testosterone.

But this experiment on guinea pigs proved that model is wrong.

Walk us through the setup.

So they took a large group of male guinea pigs.

Before doing anything, they just measured their natural sex drive.

They watched them with females.

Some were high drive, very active.

Some were medium.

Some were low.

Just their natural personality.

Okay.

Step one.

Establish the baseline.

Step two.

Castrate all of them.

And as you'd expect, the sex drive in all the groups dropped to zero.

Without the hormone, the behavior stops.

Okay.

Step three.

The replacement.

Exactly.

Now they gave all the guinea pigs the exact same dose of testosterone replacement therapy.

Now, if testosterone was a volume knob or a gas pedal, what would you expect?

You'd expect them all to have the same level of drive, right?

They all have the same amount of the drug in their blood.

Exactly.

Or you'd expect them all to go to a medium level.

But that is not what happened.

The high drive guinea pigs went right back to being high drive.

The low drive went right back to being low drive.

Even with the same amount of hormone.

Even though they had the exact same amount of hormone circulating in their systems.

That is completely counterintuitive.

So the hormone isn't the driver.

No.

The hormone is permissive.

It's like a permission slip.

You need the slip to go on the field trip.

Without it, you stay home zero drive.

But having 10 permission slips doesn't make you enjoy the trip anymore.

So the high drive animals had brains that were just more sensitive or tuned to the behavior.

Exactly.

The hormone just allowed that internal neural machinery to run.

Once you meet the minimum threshold, adding more doesn't really increase the drive.

That is a huge takeaway.

It's about the brain's sensitivity, not the hormone level.

It is.

What about females?

Is it permissive for them too?

For female rats, it's a bit different.

It's more about a specific sequence.

They need estrogen first, which makes them perceptive, interested.

And then they need progesterone, which makes them receptive, physically able to mate.

Without that specific one, two punch, you don't get the behavior.

Which leads us perfectly into section three,

the neural circuitry.

We know the hormones are permissive, but where do they go?

What parts of the brain are they hitting?

We have to trace the wiring.

Let's start with the female circuit.

For the female rat, the key behavior is lordosis.

This is that posture where she arches her back and moves her tail aside to allow the male to mate.

It's a reflex, but it's a gated reflex.

What do you mean gated?

I mean, if she doesn't do this, mating is mechanically impossible.

She controls it.

And the command center for this is the VMH.

The ventromedial hypothalamus?

Right.

A small cluster of neurons deep in the brain.

If you lesion or damage the VMH, the female will never do lordosis again.

No matter how many hormones you give her, the system is broken.

So how do the hormones affect this specific spot?

The estrogen we just talked about goes right to the VMH and it causes the neurons there to physically change.

They grow more dendrites,

the branches that receive signals.

So they're literally reaching out to connect with other neurons.

Yes.

It's like the hormone is building the road for the signal to translon.

So the signal starts in the VMH.

Where does it go from there?

Let's trace the path and figure 12 .6B.

It's a chain of command.

The VMH sends a signal to the periaqueductal gray in the midbrain.

That then sends a signal to the medullary reticular formation in the brain stem.

And that sends a signal down the reticular spinal tract to the spinal cord.

And the spinal cord tells the back muscles contract.

And you get lordosis.

Yeah.

Exactly.

It's a reflex loop, but it's gated by the brain.

The brain only lets the reflex happen if the hormones have prepared the VMH.

Okay.

So let's flip to the male circuit.

He's got a different command center.

He does.

For the male, the critical area is the MPOA, the medial preoptic area.

If you damage the MPOA in a male rat and he stops copulating.

But, and this is a really fascinating distinction, he doesn't stop Wait, how do we distinguish wanting from doing in a rat?

How do you test that?

By testing motivation versus ability.

If you put a female in a chamber where the male has to press a heavy bar or even endure a mild shock to get to her,

a rat with a damaged MPOA will still press the bar.

He still has the motivation.

Well, he'll work for it.

He'll work to get to her.

But once he's there, he can't perform the physical act.

He can't mount.

So the MPOA controls the execution, the mechanics, but the drive, the desire lives somewhere else in the brain, likely in the amygdala and other motivation and reward centers.

The MPOA is like the conductor of the physical performance.

Now there's a specific mechanism here regarding erections that I found fascinating because it involves taking your foot off the brake.

It involves a place called the PGN, the perigiganta cellular nucleus.

It's in the brainstem.

Now, normally the PGN is sending a constant stream of serotonin down to the spinal cord to inhibit erections.

Basically the PGN is the anti -erection center.

It is constantly saying no.

So to get an erection, you don't just turn on a switch.

You have to inhibit the inhibitor.

Precisely.

When the male is aroused, the MPOA sends a signal down to turn off the PGN.

It suppresses the suppressor.

And when that serotonin brake is lifted, the spinal cord is allowed to trigger the erection.

This explains a very, very common side effect of antidepressants, doesn't it?

It absolutely does.

Many antidepressants are SSRI selective serotonin reuptake inhibitors.

They work by increasing the amount of serotonin floating around in the synapse.

And since the PGN uses serotonin to inhibit erections, if you flood the system with serotonin artificially, you're essentially slamming on the parking brake.

That's why sexual dysfunction is such a common complaint with those medications.

That makes so much sense when you see the wiring diagram.

You're boosting the exact chemical that nature uses to stop.

Correct.

Okay.

Before we leave the neural stuff, we have to mention pheromones.

We mentioned the ear wiggling, but smell is huge for rats.

It is.

Rodents have a specialized organ called the VNO, the vomeronasal organ.

It's separate from the main nose, and it detects these heavy, non -volatile chemical signals called pheromones.

And that pathway goes where?

It goes from the VNO to the accessory olfactory bulb, then to the medial amygdala, and finally right to the MPOA to trigger that mating behavior.

And this leads to something called the Bruce effect, which honestly is one of the most brutal things I've read in this chapter.

It is nature being pragmatic to a ruthless degree.

The Bruce effect is this.

If a pregnant female mouse smells the urine of a new male,

a male she didn't mate with, she will often terminate her own pregnancy.

Her body just ends it.

Her body reabsorbs the fetuses, and she goes back into estrus.

But why?

That seems incredibly It's a survival calculation.

In the wild, if a new male takes over a territory, he will often kill any babies that aren't his.

It's called infanticide.

He does this to stop the female from nursing, so she'll go back into heat, and he can pass on his own genes.

So the female's body anticipates this?

Biologically, yes.

Her body knows that if a strange male is around, her current litter is doomed anyway.

So rather than waste all that energy carrying and birthing babies that will just be

It's making the best of a bad situation.

Nature is intense.

Okay, let's pivot.

Section four, human sexual behavior.

We've talked a lot about rats.

How much of this applies to us?

Well, a lot of the hormonal basics are similar.

Gasostrone is still permissive in humans,

but our behaviors are obviously much more diverse.

We rely less on reflaces and more on complex social cues.

And historically, studying this was taboo.

Right.

Alfred Kinsey in the 1940s was the trailblazer here.

He really was.

He conducted these massive surveys that just broke the silence.

He revealed that things like masturbation, premarital sex, same -sex experiences were far more common than society pretended.

He showed that sexual behavior exists on a continuum.

And then Masters and Johnson came along in the 60s and actually observed people in a lab setting.

They gave us a physiology.

They did.

They identified the four phases of sexual response.

Excitement, plateau, orgasm, and resolution.

But one of the key differences they found between men and women involves that refractory period we talked about earlier with Sooty.

Right.

Men are like the guinea pigs.

Men typically have an absolute refractory period after orgasm.

They physically cannot orgasm again for a period of time.

Women, however, do not necessarily have this.

Okay.

Many women can experience multiple orgasms in rapid succession without a loss of arousal.

And looking at the brain scans, the fMRI scans, there are some really interesting

satisfaction looks like in the brain.

Figure 12 .27 highlights this.

It's fascinating.

When men ejaculate, there's huge activity of the VTA, the ventral tegmental area.

That's the dopamine center.

It's pure reward.

It's the same area involved in drug highs or eating your favorite food.

Simple, direct reward.

Pretty much.

Yeah.

For women, orgasm activates the basal forebrain, also reward, but also the insula and the anterior cingulate cortex.

And what do those do?

Well, those are areas involved in emotional processing, pain regulation, and consciousness.

It seems to suggest there's a more complex integration of sensory and emotional centers occurring during the female climax compared to the male.

And quickly, let's address the menstrual cycle.

There's this common myth that women's sexual interest fluctuates wildly with their cycle, you know, just like an animal in estrus.

Yeah, the text busts this myth.

While there might be slight upticks in interest around ovulation for some, most studies show that women's sexual interest is fairly stable across the cycle.

Unlike the rat that only mates during estrus, human sexuality has been largely uncoupled from those strictly reproductive windows.

Which brings us to what happens after reproduction.

Section 5.

Parental behavior.

Because if you just have the baby and leave in many species, that baby dies.

Correct.

We have to distinguish between altricial and precocial animals.

Precocial animals, like ducks or horses, are born ready to move.

They can walk, they can see, they can follow mom almost immediately.

But humans are not that.

No, humans are altricial.

Like rats and songbirds.

We are born completely helpless.

Blind, naked, unable to thermoregulate, unable to feed ourselves.

We require intense, prolonged parental investment.

So how does a rat mom know how to be a mom?

Is it just instinct?

It's a mix of hormones and, well, self -stimulation.

This is one of my favorite details in the entire chapter.

Pregnant rats spend a lot of time licking their own nipples.

We used to think it was just cleaning.

But it turns out that licking physically changes the brain.

It expands the sensory map in the somatosensory cortex.

The area of the brain dedicated to nipple sensation actually gets bigger.

It makes them more sensitive.

And what's the function of that?

It prepares the milk letdown reflex.

When the pups are born and they start suckling, the mother needs to be hypersensitive to that touch in order to release milk.

If she doesn't lick beforehand, the reflex is weak.

She's literally rewiring her own brain to prepare for the babies.

And the hormones themselves are powerful enough to just program this behavior.

There's a famous experiment called parabiosis.

It sounds like something out of Frankenstein.

It does a bit.

Parabiosis involves surgically connecting the blood supply of two animals so they share a circulatory system.

And they connected a new mother rat to a virgin female rat who had never been pregnant.

So the virgin rat is getting a direct feed of the mother's blood.

Yes.

And the virgin rat suddenly started acting like a mother.

She would build nests.

She would crouch over pups.

She would retrieve them if they wandered off.

The hormones in the blood alone, estrogen, progesterone, prolactin, were enough to switch on the maternal program in her brain.

That is incredible.

It really shows how chemical these emotions or instincts can be.

It really does.

Okay.

We're about halfway through.

We've covered the behavior.

Now I want to get into the deep biology, the developmental stuff.

How do we become male or female in the first place?

Section six, sexual differentiation.

This is the organizational story.

And it all starts at conception.

The sperm brings either an X or a Y chromosome.

If you're XX, you're on the path to being female.

If you're XY, you're on the path to being male.

But that's just the genetic recipe.

The cooking happens later.

I like that analogy.

So early on, the fetus has what the text calls indifferent gonads.

They could go either way.

Exactly.

Up until about six weeks in humans, we are all physically identical.

The gonads are totally unisex.

The deciding factor is a single gene on the Y chromosome called SRY.

SRY.

Sex Determining Region of the Y chromosome.

If you have this gene,

the indifferent gonad turns into a testis.

If you don't have it, the gonad turns into an ovary.

That is the first domino to fall.

Okay.

So SRY makes a testis.

Now the testis starts working and it has two jobs, right?

Two very specific jobs.

It acts as a factory producing two things, testosterone and AMH, which is anti -malarion hormone.

Okay.

Let's break those down.

What does testosterone do here in the fetus?

In the fetus, you have two sets of plumbing just waiting in the wings.

You have the Wolfian Ducks, which is the male potential, and the Malarian Ducks, the female potential.

Testosterone tells the Wolfian Ducks to develop.

They become the epididymis, the vas deferens, all the internal male plumbing.

And AMH, what does that do?

AMH tells the Malarian Ducks, the female plumbing,

to wither away.

It actively causes them to disappear.

So to become male, you have to hit the gas on the male stuff.

And D, hit the brakes on the female stuff.

Exactly.

If you only did one, you'd end up with a mix of both.

But we're not done.

That's just the internal plumbing.

What about the external genitalia, the penis and scrotum?

I just assume testosterone did that too.

It helps.

But regular testosterone actually isn't strong enough to form the external genitals on its own.

You need a supercharged version called DHK dihydrotestosterone.

How do you get that?

There's an enzyme in the genital skin called 5 -alpha reductase.

It grabs the testosterone and converts it into this much more potent DHT.

And the DHT is what actually shapes the penis and scrotum.

So it's a relay race.

SRY makes testes.

Testes make testosterone and AMH for the internal plumbing.

Then that testosterone gets converted to DHT for the external part.

You got it.

That's the sequence.

And for females?

The female route is often described as the default because it doesn't require an active on switch like the SRY gene.

If there is no SRY, you get ovaries.

And the ovaries don't make testosterone and they don't make AMH.

So what happens to those two sets of ducts?

Without testosterone, the male wolfian ducts just wither and die.

And without AMH to stop them, the female malaria ducts survive and grow into the uterus and the ova ducts.

So nature builds female unless it's actively told otherwise?

In a manner speaking, yes.

The abscess of that male hormonal signal results in the female form.

Now this system is elegant, but it's complex.

And because it's complex, things can happen differently.

This brings us to section seven, intersex conditions.

This is where we see what happens when one of those dominoes doesn't fall quite right.

And these cases are incredibly eliminating for science.

Let's look at CAH congenital adrenal hyperplasia.

This affects XX individual.

Right.

Genetic females.

They have ovaries.

But their adrenal glands, which sit on top of the kidneys, have a malfunction where they pump out massive amounts of androgens, which are male hormones during fetal development.

So they have the female genetic blueprint, but they're being flooded with male hormones from a different source.

Exactly.

And remember, those hormones shape the external genitals.

So these girls are often born with what looks like an intersex appearance, typically a large clitoris that might resemble a penis or fuse labia that look like a scrotum.

It just shows that even with XX chromosomes, hormones can physically masculinize the body.

Then there's the opposite situation, AIS androgen insensitivity syndrome.

This one fascinates me because it's like a broken receiver problem.

AIS is essentially the gas pedal is disconnected scenario.

These individuals are XY.

They have the S R Y gene.

They have testes inside their abdomen and the testes are making plenty of testosterone.

So hormonally they are male.

Yes.

But due to a genetic mutation, their body lacks the receptor for testosterone.

It's like screaming a message at someone who is deaf.

The cells cannot hear the testosterone signal.

So what happens to the body?

The body follows the no signal route.

Without the ability to sense testosterone, the Wolfian ducks die away.

The external genitals develop as female.

They grow breasts at puberty.

They have a vagina.

They look like women.

They're usually raised as girls.

But they have tests inside them.

Yes.

Usuland ascended.

And because the testes did make AMH, the anti -malarion hormone, the female internal organs like the uterus and ovaries withered away.

So they are infertile.

So they are genetically male, hormonally male, but physically they develop as female because they can't process the hormone.

Yes.

And typically they identify as women, which tells us something really interesting about gender identity and hormones.

Even though their brain was bathed in testosterone, if the brain's receptors were also broken, the brain didn't masculinize.

And the third condition, this is the one that relates to that exit 12 nickname, the govidoses.

This is a specific population in the Dominican Republic.

These are XY individuals who have a genetic mutation.

They lack that enzyme we talked about, five alpha reductase.

The one that makes the super testosterone, DHT.

Right.

So in the womb, they have testosterone.

So their internal male plumbing, the vas deferens, develops, but they can't make DHT.

So their external genitals don't masculinize.

They were born looking like girls.

They're raised as girls.

And then puberty hits.

Exactly.

At puberty, the testes produce this massive surge of regular testosterone.

And at high enough levels, regular testosterone can finally do the job that DHT usually does in the womb.

Their voice deepens, muscles grow, the phallus grows into a penis.

The testes descend.

They physically transform into men.

Hence, govidoses eggs or testicles at 12.

Exactly.

And socially, most of them transition to living as men, which suggests that the early testosterone exposure on the brain might have already happened, even if the body didn't show it yet.

That is a perfect segue.

We've talked about the body.

Now, the big question, does this same process happen to the brain?

Section eight, sex on the brain.

This is the concept of sexual dimorphism in the brain.

Are male and female brains structurally different?

And the answer is yes, in very specific areas.

Let's look at songbirds first.

In canaries, the male sings to attract mates.

The female doesn't.

And if you look at their brains, the areas controlling song places called the HVC and RA are five to six times larger in the male.

That is a huge structural difference.

And in rats, there's the SDN -POA.

The sexually dimorphic nucleus at the preoptic area.

It's much, much larger in males.

And we know this is caused by hormones because if you castrate a male at birth, his SDN ends up small, like a female's.

If you give a female testosterone at birth, her SDN grows large.

It is organized by the hormone early in life.

But here comes the plot twist, the aromatization hypothesis.

This is the part that sounds like a total contradiction.

It is completely counterintuitive.

In rats, the hormone that actually masculinizes the brain is estrogen.

Run that by me again.

Estrogen, the so -called female hormone, makes the rat brain male.

Yes.

Here's the mechanism.

The fetal tests produce testosterone.

Testosterone travels in the blood up to the brain.

Once it gets inside the brain neurons, an enzyme called aromatase converts it into estradiol, a form of estrogen.

And it's that estrogen that binds to DNA and organizes the male brain.

But wait, females have estrogen.

They get it from their mothers.

Why doesn't the female rat's brain get masculinized?

Because of a biological shield.

The fetus produces a protein called alpha -fetoprotein that circulates in the blood.

This protein binds to estrogen and creates this big complex that's too large to cross the blood -brain barrier.

It prevents the mother's estrogen from getting into the brain.

So the female estrogen is blocked at the gate.

But testosterone?

Testosterone ignores the shield.

It slips right through the blood -brain barrier, gets inside the neuron, and then it gets turned into estrogen safely behind enemy lines.

It's a Trojan Horse strategy.

That is incredibly sneaky.

Now, the big caveat here, does this happen in humans?

And no.

And this is very important to stress.

The aromatization hypothesis is for rodents.

In primates and humans, this mechanism does not appear to be the primary driver.

Men with genetic mutations that prevent them from making or sensing estrogen still have masculine gender identities.

So for us, it's the androgens acting directly.

It seems so.

But it just shows how diverse nature's toolkit can be.

I want to touch on one more neural thing.

The SNB.

The spinal nucleus of the vulva cavernosus.

This is a story about use it or lose it.

Right.

The SNB controls the muscles of the penis.

Both male and female rats start out with these neurons in their spinal cord.

But in females, they die off during development.

In males, testosterone saves the muscles, which then send a trophic factor, like a lifeline signal, back to the neurons to keep them alive.

But there's a social twist here regarding the mother rat.

Yes.

This is fascinating.

Mother rats lick the genital area of their male pups more than their female pups.

They can smell the testosterone metabolites in the urine.

And that licking stimulation actually helps save those SNB neurons.

How do we know that?

If you block the mother's sense of smell, so she can't tell the difference, she licks everyone less.

And the males in those litters end up with fewer neurons in the SNB.

So the mother's behavior of social interaction is physically changing the structure of the baby's spinal cord.

Exactly.

It completely blurs that line between biology and socialization.

The social interaction becomes biology.

That leads us to the final frontier.

Section 9.

Human dimorphism and sexual orientation.

If hormones shape the body and the brain, do they determine who we are attracted to?

This is a sensitive and complex topic, but the science is pointing towards strong biological underpinnings.

We have to talk about the INAH3.

The Lave study from the 90s.

Simon Lave looked at this specific nucleus in the hypothalamus, and he found that INAH3 was larger in heterosexual men than in women.

But interestingly, in gay men, it was smaller, more similar in size to women.

Now we have to add the context here.

This is a correlational study.

Correct.

And Lave was always very careful about this.

He acknowledged that we don't know if this size difference is the cause of homosexuality or a result of it, or if the AIDS virus, which was the tragedy of that era, played a role.

However, later studies on animal models do suggest this area is influenced by prenatal hormones.

And there are other markers that seem to be set before birth.

Things that don't change, like finger length.

Yes, the 2D .4D ratio.

Generally speaking, men tend to have a ring finger, the fourth digit, that is longer than their index finger, the second digit.

In women, they tend to be closer to equal length.

And this ratio is determined by your prenatal testosterone exposure in the womb.

And the findings regarding orientation.

Studies have shown that lesbians, on average, have a more masculine finger ratio, indicating higher prenatal androgen exposure.

We also see differences in otoacoustic emissions, faint sounds that ears make, which are stronger in women, but weaker and more male -like in lesbians.

So this suggests that for lesbians, prenatal hormones might play a significant role.

What about gay men?

The androgen markers are less clear for gay men.

But we do see strong genetic signals.

There's the fraternal birth order effect.

This one is so bizarre.

The more older brothers a man has, the more likely he is to be gay.

Specifically for right -handed males, yes.

The probability increases by about 33 percent for each older biological brother.

The leading theory is the maternal immunization hypothesis.

The idea that when a mother carries a male fetus, her body is exposed to male -specific proteins, HY antigens.

Her immune system might recognize these as foreign and build antibodies.

With each subsequent male pregnancy, that immune response gets stronger, and those antibodies might cross the placenta and affect the development of the fetal brain.

So it's not genetics from the father, but a biological reaction in the womb's environment.

Exactly.

It's estimated that about one in seven gay men can attribute their orientation to this specific effect.

And there's also the XQ28 genetic region, which seems to play a role in some families.

Which brings us full circle.

Back to Bella.

Or Benjamin.

Yes.

Remember, Benjamin was raised as a girl, but when they transitioned to male, they noted something very important.

Even when living as Bella, they were attracted to females.

So the prenatal testosterone that Bella had before the surgery seems to have wired the brain for attraction to females, regardless of how she was raised.

That's the implication.

And in a larger study of 14 cases like Bella's children, born with cloacal atrophy and raised as girls, eight of them eventually declared themselves boys.

That's more than 50 percent.

Compared to the general population, that is an overwhelming signal that prenatal exposure to androgens creates a powerful predisposition for male gender identity and attraction to females.

But we have to look at the other side of that number.

Five of them stayed living as females.

They did.

Which means five out of 14 were content with the gender that was assigned to them by their parents.

This tells us that socialization does matter.

It's not a hundred percent biology.

It's not destiny.

We are a mix.

So let's wrap this up.

We've covered a lot from peacocks to guinea pigs to human brain scans.

What are the big takeaways here?

I think first, reproduction is a complex staged behavior.

It's not just an act.

It's a whole sequence of attraction, appetite, and mechanics all driven by these deep evolutionary pressures.

Okay.

Second, hormones are dual purpose.

They organize the brain in the womb, setting up the hardware, and they activate behavior in the adult.

They're both the architect and the power switch.

And third,

that the binary of male and female is the most common outcome.

But nature has many variations,

intersex conditions, differences in brain wiring, variations in orientation.

And these aren't errors so much as they are demonstrations of just how complex the developmental recipe really is.

It really makes you think about that rat mom licking our pups.

It does.

And that's the thought I want to leave the listener with.

We often get into this fight about nature versus nurture.

But if a mother's touch, which is nurture,

can physically save neurons in the spinal cord and change the brain, which is nature,

then the distinction is an illusion.

Our experience becomes our biology.

Deep stuff.

As always, thank you for joining us on this dive into the machinery of who we are.

It was my pleasure.

And a warm thank you from the Last Minute Lecture team for tuning in.

We'll see you on the next Deep Dive.

Stay curious.