Brain development: The most important sexual organ

That's the title of an article in Nature dated January 2004. Funnily enough, I'd missed it, it didn't seem to have much relevance at the time....

New evidence suggests that the brain begins to develop differently in males and females much earlier than was thought — before sex hormones come into play.
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...biologists are now starting to realize that hormones aren't the only significant determinant of the brain's sexual destiny. Indeed, male and female brains may even start moving down different developmental paths before sex hormones are produced in significant quantities. "There is plenty of evidence that hormones organize the brain sexually, but it's not the whole story," says Eric Vilain, a geneticist at the University of California, Los Angeles (UCLA).

New findings about the genetic and other factors that influence the brain's sexual development could do more than simply rewrite the textbooks. They might provide insights into conditions such as transsexualism — and perhaps eventually lead to tests that could determine whether a baby with an intersex condition is more likely to grow up thinking, feeling and behaving like a man or a woman.
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Studies of the non-hormonal influences on the sexual development of the mammalian brain are at an early stage. But Vilain is already trying to apply this emerging knowledge to the phenomenon of transsexualism — where individuals are physically and genetically one sex but perceive themselves to be members of the other. Reports of the condition sometimes running in families11 have led some researchers to speculate that genetic factors may be involved. "Some of the genes differentially expressed in the brains of male and female mice may be altered in transsexuals," Vilain suggests.

He is now collaborating with Vincent Harley, a molecular biologist at Prince Henry's Institute of Medical Research at the Monash Medical Centre in Melbourne, which runs the largest transsexual clinic in Australasia. They are looking for variants in the sequence of these genes to see if some are more common in transsexuals than in the general population. Their initial analysis will focus on three genes, located on the sex chromosomes, that are known to encode proteins that regulate the activity of other genes.

Such research into the genetics of gender identity is inevitably controversial — especially given the dark history of the eugenics movement, which viewed conditions such as transsexualism as 'diseases'. But Harley has been overwhelmed by the positive response from the transsexual community since the study began. "I've had people e-mailing me to offer their help," he says. "There is a stigma that transsexualism is a lifestyle choice. It may be very liberating to them if we can show that there is a genetic or biological basis." Indeed, Harley has been invited to give talks about his research to transsexual groups in Melbourne.

Hmmm... sounds as if I should give them a call....