Testosterone’s Sidekick

Hormones have long been considered the solo act that molds brains along gender lines. But in recent years, hints that certain genes on the sex chromosomes might also play a role have been emerging. Now, new research points to the first structural brain difference between male and female mammals attributed to genetics alone.

Sex hormones, in particular testosterone, help shape the developing brain of fetuses and newborns. Testosterone, secreted by the gonads, makes male brains distinct from female ones, and it is thought to account for difference in behavior and brain structure. A group of scientists, though, has wondered for years whether genes on the X and Y chromosomes have a hand in shaping brain differences. To find out, neuroendocrinologist Arthur Arnold at the University of California, Los Angeles, collaborated with colleagues in the United Kingdom who had genetically altered mice.

Robin Lovell-Badge and Paul Burgoyne, developmental geneticists at the Medical Research Council's National Institute for Medical Research in London, performed a genetic sex change. By using mice with a deletion in their Y chromosome for a gene called Sry, which kick-starts testes development, they ended up with XY “females” that had ovaries; adding Sry to the genomes of females generated XX "males" with testes. Although these mice had fully developed sex organs, both groups had fertility problems due to the gene manipulations.

Arnold and his colleagues then compared behaviors and brain structures with normal mice of both sexes. They found that sexual and social behaviors depended on the presence or absence of testes. But one brain structure differed by chromosomal makeup--in other words, XY animals with ovaries were distinct from XX animals with ovaries. Among the XYs, axons of nerve cells containing the hormone vasopressin, whose function is associated with aggression, among other characteristics, were up to 19% more densely packed. The fibers are known to be more prevalent in males, but the difference had been wholly attributed to testosterone, not genes. The research is reported in the 15 October Journal of Neuroscience.

"This is the beginning of a larger story," predicts Bruce McEwan, a neuroendocrinologist at Rockefeller University in New York City. Stephen Maxson, a behavioral geneticist at the University of Connecticut, Storrs-Mansfield, agrees that the fiber density differences are striking, although he wonders whether other brain differences attributable to sex chromosomes will be found.

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