Your Default Brain Is Female
By: Taylor Mitchell Brown
Tags: Neuroscience, Gender, LGBTQ, Science, Transgender

Your brain and the pancreas aren’t much different. Both are formed prenatally, both are bodily organs, and both interact with the rest of anatomy to give us complex physiological systems. But, unlike the pancreas, the brain also gives us sex.

Sexual differentiation in the brain is the product of a long journey through prenatal development. This journey starts in the DNA, moves to our sex organs, then shapes the rest of the body from there. This shaping organizes our anatomy along male and female lines.

There’s diversity, however, in the way we express these male and female traits. Some of us are male, yet not too masculine, and others of us female, yet not too feminine. Some of us don’t identify with any known gender. Curiously, many of these differences emerge from small modifications to a female default.

Undifferentiated

Early in gestation (i.e., the womb), there are few differences between the sexes. Our growing anatomy is undifferentiated and essentially ambiguous. The differentiation begins to unfold around week nine. Here, the gonads turn into testes or ovaries, a change that initiates the rest of sexual differentiation.

Whether we get testes or ovaries is determined by our genes — more precisely, our sex chromosomes. Genetic females have an XX pair, which supplies the genetic material to become women, while males have an XY pair, supplying the material to become men. (While you can have an extra X or Y chromosome, which would make you a trisomy, I won’t discuss that here.)

Specifically, it’s the Y chromosome that does the heavy lifting; it carries a gene that codes for testes. Conveniently, in an act of felicity uncommon to biology, geneticists call this gene the sex-determining region of the Y chromosome. Called the SRY gene for short, this small patch of DNA skews gonadal development in the male direction.

Without an SRY gene, the gonads follow the female path — they turn into ovaries. We can replicate this experience in many mammals, inducing a mutation that renders the gene mute. The result of this mutation is always the same: ovaries. The SRY gene, then, is the first way in which development is biased female.

A Move from Default

We call this default pathway feminization. This is the trajectory we follow without an SRY gene. To get us anything other than this, we have to undergo two separate processes: defeminization, the suppression of this female default, and masculinization, the active construction of male traits.

Defeminization and masculinization influence everything from our sexual orientation to the behavior we express in childhood. The first thing they do is differentiate the reproductive tract. The second thing they do is shape the brain. Here’s a little more on the specifics:

Defeminization . This process prevents the development of a female reproductive tract and other naturally unfolding female parts. This includes the uterus, vagina, and fallopian tubes.

. This process prevents the development of a female reproductive tract and other naturally unfolding female parts. This includes the uterus, vagina, and fallopian tubes. Masculinization. This creates male reproductive organs wherever the female default was suppressed. The result is a penis, scrotum, epididymis, and vas deferens — but also a male brain.

Each of these processes is governed by the hormonal milieu secreted from the testes. Masculinization is due mostly to testosterone, while defeminization is due to a few other hormones. Both processes are necessary to get us anything other than female.

Incompletely Masculinized

Sometimes masculinization and defeminization don’t work as intended; they suffer a kink that causes them to unfold incompletely. The result of such kinks is a mixture of male and female traits — masculinization in some places, feminization in others. Androgen insensitivity is one way in which we get such mixtures.

Androgen insensitivity is exactly what it sounds like — the person’s body is unresponsive to androgens. Typically, this is because the receptor for said androgens is defunct, possessing a mutation that renders it difficult to bind to. The disorder is only salient in genetic males, since they’re the ones that produce most of the testosterone.

Androgen insensitivity exists along a spectrum. It can either be complete, in which case the androgens can’t bind to the receptor at all, or partial, in which case some binding can occur. The effects of the disorder are commensurate to the functionality of the receptor.

Males with complete androgen insensitivity generally identify as women; their testes don’t drop, they develop a vagina, and from all external appearances look female. Sometimes they don’t realize they’re a genetic male until later in life when they face reproductive issues. Because they still have testes (which secrete other defeminizing hormones), certain parts of the reproductive tract don’t differentiate correctly. The result is infertility.

Partial androgen insensitivity yields something a little more complex. Those affected often present with ambiguous genitalia, sometimes a “micropenis,” and are more likely to experience gender dysphoria, a feeling of psychological discomfort with the body they inhabit. This happens regardless of the gender in which they were raised.

In aggregate, androgen insensitivity shows what happens when a genetic male doesn’t masculinize. Either the result is total, in which case most of the body develops female, or partial, in which case you get a mixture of male and female traits. Either way, this lack of testosterone causes the body to feminize.

The Default Brain

Without the hormones secreted from the testes, feminization will continue unabated. You’ll get a female reproductive tract, female reproductive organs, and all the other bells and whistles of a female reproductive anatomy. But you’ll also get a female brain.

The process of feminization in the brain is generally one of automated self-destruction through a process called apoptosis (the second “p” is silent). Since at birth — with one minor exception — we’re born with all the neurons we’ll ever have, this destruction yields lifelong consequences for the size and shape of many parts of the brain.

Some of the regions affected by this treatment make total sense. The spinal nucleus of the bulbocavernosus, for instance, which projects motor input from the brain to the penis, withers in genetic females. To survive, it needs more testosterone.

Other regions affected by this treatment make a little less sense, yet still demonstrate how male and female brains come to differ. I’ll mention two of these: the hippocampus, which is involved in learning, memory, and spatial reasoning, and the locus coeruleus, which is involved in stress and fight or flight.

Hippocampal volume shrinks without prenatal testosterone. This is why men, on average, have larger hippocampi than women — genetic females don’t produce enough to keep it as large. This difference is often used to help explain the disparity in male and female spatial reasoning.

The locus coeruleus, in contrast, thrives in genetic females. This is why women, on average, have larger loci coerulei than men. It also helps explain why men suffer a higher percentage of stupidity-induced deaths from things like accidental injuries and violence: their stress responses are defunct, so they’re less intimidated by reckless and stupid things.

Without testosterone, this differentiation veers in the female direction: you get a smaller hippocampus, a larger locus coeruleus, and very few neurons in the spinal nucleus of the bulbocavernosus. With testosterone, you get the opposite.

More than Female

Testosterone is the primary masculinizing hormone in the brain. While its presence is far greater in males than in females, there are certain disorders that can give females comparable amounts. One such disorder is congenital adrenal hyperplasia.

Congenital adrenal hyperplasia is the most common autosomal disorder, affecting one in every 2,000 women. It results from a defect in the biological system that produces cortisol, a stress hormone derived from the adrenal glands. This defect causes the brain to secrete more precursors to cortisol in an attempt to establish normal physiological amounts. The problem is, these precursors also cause the adrenal glands to secrete more testosterone (something they produce naturally but not in great volume). As a result, affected genetic females get masculinized.

Like androgen insensitivity, congenital adrenal hyperplasia exists on a spectrum. There’s both a classic version, in which case the defect causes a total dissolution of cortisol production, and a nonclassic version, wherein most of the production is preserved. Since nonclassic versions don’t manifest until later in life, they won’t affect prenatal sexual differentiation.

Classic versions of congenital adrenal hyperplasia trigger significant masculinization: you get a penis, diminished desire for heterosexual relationships, more male-typical behavior, and experience less satisfaction with the female sex category. But you also get a male brain.

Genetic females with congenital adrenal hyperplasia get a larger hippocampus, a smaller locus coeruleus, and increased spatial reasoning over that of their unaffected brothers and sisters. These changes are proportional to the amount of testosterone they experienced prenatally.

Congenital adrenal hyperplasia, then, illustrates what can happen when genetic females are masculinized by testosterone. If severe enough, most of the body will develop male. If less severe, the changes won’t really show. Either way, testosterone will push anatomy in the male direction.

Know Your Body

It’s imperative that we understand how sexual differentiation takes place in the prenatal environment. Why, you might ask? Because current surgical practices tend to favor some ugly outcomes.

With both androgen insensitivity and congenital adrenal hyperplasia, for instance, many of those affected are born with ambiguous genitalia. In response, surgeons will often opt for feminization surgery, giving the affected person female sex organs. The problem is, these genitalia don’t necessarily match with the person’s felt identity.

As we saw, both disorders tweak the brain along with the rest of the body. Partial androgen insensitivity yields something between a male and female brain. Congenital adrenal hyperplasia does the same. In neither case does feminization surgery seem likely to match the external sex with the internal.

It’s not a coincidence that rates of gender dysphoria are greater in these two populations than in the general public. If your external genitalia are pressed to fit a shape that doesn’t match your internal identity, it makes sense that dysphoria would follow. (We also, however, live in a society where such people are stigmatized, which contributes to the dysphoria.)

Our goal, then, should be to understand this differentiation as clearly as we can. This will allow us to appropriately align the sex organs — if they even need to be aligned — with whatever identity the person will ultimately develop. Then, we will be able to employ practices that minimize the amount of dysphoria in the world. But until then, at least we all now know that our brains are by default female.