April 23, 2010

Genes, hormones, sex and gender identity

What does modern biology tell us about sex and gender? I have done some reading for you.

When working on my blog posts on Gilmartin's love shy male lesbians, I realized that I have never really tried to get to the bottom of what modern biology has to say about sex and gender.

In my post on What brain science says about M2F transsexuals I presented some recent research on various nuclei (brain sectors) that may or may not govern sexual orientation and gender identification.

Given that I am planning to present Gilmartin's explanation for the existence of male lesbians in my next post, I believe it could be useful to have a popular summary of what contemporary science says about genes, hormones, sex and gender.

And as always: These are theories being constantly revised by the scientific community. Do not read this as the final word on the biological basis for sex and gender.

The life of the fetus

There are several variables that influence the sexual orientation and the personality of the fetus. We all know about the sex chromosomes (XX for women and XY for men). What many do not know is that only a small number of sex differences are directly caused by the sex chromosomes.

The majority of sex differences are thought to be not sex linked, but sex limited. They are caused by genes that are present in both sexes. This means that men have most of the sex and gender relevant genes women have (and visa versa). Potentially an XY "male" can develop practically all of the traits that define a biological woman.

These sex difference genes can be dichotomous (which is a fancy word for an on/off switch) or they can be continuous, which large variation between two extremes. The combination of all the sex limited genes forms the biological basis of the sex identifying aspects of a personality.

I like to picture this as a huge audio mixing table of the kind they use to produce records. There are on and off switches to open or close channels and tracks. There are sliders to adjust volume, frequency, dynamics, and panoramic position. And there a buttons for special filters and effects. One slider may also be the slave of another. This means that the adjustment of one slider will make another one move as well.

In a similar (but not identical) way nature uses genes, hormones and hormone receptors to produce the unique "mix" of a human being. Some of us come out as R&B, others as hard rock and some as melancholy blues.

The modern sex narrative

The traditional narrative these days is that the male Y chromosome has a gene complex called TDF (the Testes Determining Factor). The TDF has a gene called SRY (Sex Determining Region of the Y-chromosome. Duh!).

The TDF acts as a trigger that turns on genes that are found on the non-sex specific chromosomes, the ones that controls the development of the male testes.

All embryos -- male or female -- have the genes that encode the blueprint for both male testes and female ovaries. If the TDF is not there, the genes that encode the blueprint for the ovaries will turn on instead. You can say that the female bodyplan is the default. We are all girls before the TDF swings into action, according to this story.

Roughgarden's more complex narrative

Joan Roughgarden (who I presented in my Sex, Gender, Nature series) argues that this narrative is too simple, and that the SRY can only partly influence gendered presentation.

She (and many other biologists) argue that the sex of an embryo is evident even before the gonads differentiate into ovaries or testes. The gonads can develop at least partially into testes on their own, even without the SRY.

There are other mammals and vertebra that do not have the SRY, but that develop testes all the same. Moreover, the SRY is changing fast from an evolutionary perspective, and varies a lot within specific species, homo sapiens included. What nature considers "masculine" varies.

But she also agrees that the SRY is important. And truth to be told, also the "traditionalists" agree that the SRY is not alone in switching on the process that gives men testes.

Making testes

Roughgarden gives the following explanation. (Evolution's Rainbow p. 199. Do not get caught up in the names and abbreviations. This is only to give you an impression of how damned complex these processes are):

1. The gene WTI prepares the genital ridge and adjacent kidney area. Then the genes SF-I and WTI together urge SOX9 to make a testis. SOX9 is found on a non-sex chromosome. It is not part of the male Y-chromosome.

2. In girls the "anti-male" gene DAX-I intervenes, preventing SF-I and WTI from activating SOX9, so an ovary forms instead. This is one of the reasons Roughgarden is skeptical towards the idea that the default body plan is female. In this case you may say that default is male, and DAX-I must be turned on to make a girl.

3. In males, SRY inhibits DAX-I, permitting SF-I plus WTI to activate SOX9, which in turn produces a testis.

In Roughgarden's words:

"The SRY stops a gene, DAX-I, which itself was stopping testis development according to SOX9's recipe. Wow, not simple. Notice that SRY and DAX-I don't contribute materially to the recipe for making a testis. They are at the conference table just to argue, like genetic lawyers." (p. 200)

Note that even if SRY manages to get the body to produce a testis, which again produces testosterone, the battle for male-hood has not been won:

"The genetic bureaucracy may partially implement the legislation by ensuring that testosterone has only little effect, or it may fail to implement the legislation at all, as in the case of complete androgen insensitivity." (p. 201)

An XY individual with complete androgen insensitivity will appear as fully female, as the lack of testosterone receptors means that process of masculinisation never gets going.

A Y does not a man make

Here's a comment made by Eric Vilain, an assistant professor of Human Genetics at UCLA:

"We know that, there are a number of babies born who are male-they have two testes and penis - and yet they do not have a Y chromosome. We started to decipher the molecular mechanisms that lead to this situation and we now know that there [are] a few other genes that can sometimes mimic the action of the genes in the Y chromosome. So the Y chromosome is not this single force that pushes the whole male sex determination pathway."

Vilain also makes the following comment that supports Roughgarden's argument:

"The idea is in instead of having a simplistic mechanism by which you have pro-male genes going all the way to make a male, in fact there is a solid balance between pro-male genes and anti-male genes and if there is a little too much of anti-male genes, there may be a female born and if there is a little too much of pro-male genes then there will be a male born. We [are] entering this new era in molecular biology of sex determination where it's a more subtle dosage of genes, some pro-males, some pro-females, some anti-males, some anti-females that all interplay with each other rather than a simple linear pathway of genes going one after the other which makes it very fascinating but very complicated to study."


Ok, back to the traditional narrative (the one were we all start out as female):

The fetal gonads (testes or ovaries) produce hormones, primarily testosterone in the testes and estrogen in the ovaries. The testes also produce a hormone called MIS (Mullerian Inhibiting Substance or Anti-Müllerian hormone). The MIS causes the regression of internal female genitalia (defeminization). The testosterone leads to development of male genitalia (masculinization). No specific hormone is needed to develop the female genitalia. They are the default.

So a man becomes a man through two processes: a process that removes the female genitalia, and -- presumably -- also reduces some feminine traits (defeminization), and one process that generates male genitalia and encourages male traits (masculinization).

The hormonal balance produced by the testes or the ovaries is not dichotomous (an on/off variable). The amount of hormones will vary from fetus to fetus, and that variation will influence the development of the fetal brain and the "sex mix" of that individual. It seems the hypothalamus is organized differently in males and females.

Hypothalamus etc.

The hypothalamus controls the pituitary gland, which again controls hormone production in other glands. Because of this fetal brain development may also influence the future production of sex hormones in the body, and through this also future sex differences.

But that is not all: The hypothalamus also governs various natural drives, including hunger, thirst and sex drives. Different aspects of the sex drive (like sexual orientation and sex drive intensity) are regulated by different nuclei (sectors) of the hypothalamus. Many researcher believes that the basis for gender identity is also found here.

Other parts of the brain may also respond to sex hormones, and some researchers believe these are relevant to the development of brain lateralety, visuospatial learning, spatial memory, aggression, motor activity, exploratory activity etc, which all are associated with typically male and female abilities according to this line of research.


Studies of birds and rats show that their gender behavior may be changed by giving them hormones or by removing certain parts of their brain.


"When pregnant female rats are stressed in the laboratory by shining bright lights on them all day long, the male embryos in the litter produce less testosterone during their fetal period. They wind up with smaller clusters of nerve cells in the preoptic area and fewer nerve cells in the spinal cord for control of the penile muscle." (p. 225)

When testosterone drives feminization fantasies

It is important to notice that there are two sides to the effect of hormones: hormone production and hormone receptors. It does not matter if the hormone production is normal, if the receptors are lacking or react differently. This adds another dimension to the complex interplay between genes, hormones and sexual development.

The psychologist Anne Vitale has speculated on the role of testosterone as a driver for feminization urges among some M2F transgender. This may sound completely counter intuitive, as testosterone is the hormone leading to a masculinization of the fetus and the grown man.

She argues that her observations of her own patients lead her to believe that a subset of genetic males appear to respond to testosterone in a manner that evokes an overwhelming desire to express feelings of femininity.

She notes that male patients with gender dysphoria who get estrogen often find that their anxiety and their desire to cross-dress subsiding. On the other hand, F2M transgendered find that an increased intake of testosterone makes them feel better.

Vitale says:

"It is beyond dispute that there are both androgen and estrogen receptors in the brain. Genetic males normally have more active androgen receptors than women and women have more active estrogen receptors then men. That this 'normal' distribution of estrogen and androgen receptor cells can be different in some individuals appears to be a possibility. It therefore follows that androgenic and estrogenic compounds will result in a modified-to-counter expected behavior in affected individuals. For reasons beyond the scope of this Note and as counterintuitive as it may seem, it can only be assumed that testosterone plays a crucial role in forcing certain male individuals to crossdress and experience femininity to the maximum degree possibly."

To add my own 2 cents: If testosterone plays a role in sexual arousal (and it most likely does), then an increase of testosterone will make M2F crossdreamers horny. But at least parts of their "wiring" is feminine, so the resulting arousal leads to feminization fantasies instead of the stereotypical "Me Tarzan, you Jane" behavior.

If you change the testosterone/estrogen balance by adding estrogen and/or anti-androgens, the sex drive diminishes and the feminization fantasies become less urgent. The brain remains as feminine as ever, though. Taking estrogen does not "cure" you.


The point of telling you all this is that concepts like sex and gender are highly complex even before you start talking about upbringing and the effects of the surrounding culture.

The confusion and dysphoria felt by crossdreamers regarding their gender identity are likely caused by a combination of genes, hormones and receptors that lies at the outskirts of the statistically normal distribution. Given that our culture has no language or roles that could help these men and women, they find it hard to make sense of their fate.

Roughgarden says this about the gender flexibility of a system based on XX and XY chromosome configuration:

"Although the genetics of transgender expression are unknown and, in human at least, may be superseded by late embryonic and early post-natal developmental experience [i.e. non-genetic influences], transgender bodies are fully consistent with an XY system of sex determination. Indeed feminine males might easily be feminine enough, and masculine females masculine enough, to count socially and to identify as women and men, respectively, even though they possess XY and XX bodies." (pp. 214)

Nature and nurture

In addition to the effects of genes and hormones recent research also indicates that human development may be even more complex than this story seems to tell us.

First of all genes are not stable. They can be turned on and off due to external factors. Secondly the mental state of a person, which again is influenced by his or her life situation and quality of life, does influence hormone production.

But that is not all. It turns out that the brain is much more flexible than originally imagined by researchers. They now talk about the plasticity of the brain. The brain is changing according to the way we use it. To what extent this may influence our sexuality or gender identity is unknown.

What is clear is that any simple explanation of gender identity is bound to be wrong. There is no one to one relationship between one factor (being that the X and Y chromosomes, one brain area or one feminine or masculine "essence") on the one hand and sexual orientation and gender identity on the other.

Nature is a DJ

Let me get back to the mixing table metaphor. Nature is a record producer that loves variation. There are not two human beings that are completely identical, not even identical twins. Every human being is a unique remix of the song of humanity. Sexual reproduction is important, as it makes the mixing possible, but Nature does not give a damn about our understanding of gender roles.

When mixing a biological male, she may turn up a sufficient number of female tracks to make "him" feel and think more like a woman than like a man.

Indeed, when you think about it, there is not one man around that is completely masculine, regardless of what cultural template you are basing your benchmark on. The Dalai Lama is clearly a man, but shows a kind of compassion that is often identified as typical female. Margaret Thatcher and Hillary Clinton are both women, but both show an agressiveness and a determination that are often recognized as male.

That being the case, it is not hard to imagine a tipping point where the "feminine" sides of a man become so strong that he is, in fact, a woman, regardless of what "he" has between his legs. At that point "he" does indeed become a woman trapped in a man's body.


Discuss crossdreamer and transgender issues!