Testosterone

Men and women may be equals, but they often behave differently when it comes to sex and parenting. Now a study of the differences between the brains of male and female mice in the February 3rd issue of the Cell Press journal Cell provides insight into how our own brains might be programmed for these stereotypically different behaviors.

The new evidence shows that the sex hormones – testosterone, estrogen, and progesterone – act in a key region of the brain, switching certain genes on and others off. When the researchers tinkered with each of these genes one by one, animals showed subtle but important shifts in individual sex-specific behaviors, such as how males mate or females care for their pups.

"What this means is that complex behaviors like male mating or maternal care in mice can be deconstructed at the genetic level," said Nirao Shah of the University of California, San Francisco. The findings present a cellular and molecular representation of gender that is remarkable in its complexity, the researchers say.

Shah's team made these discoveries after screening mouse brains for genes that show differences in expression in males versus females. The researchers focused specifically on the hypothalamus, a region previously implicated in the control of sex-specific behaviors. Their screen produced a list of 16 genes with clear sex differences in distinct neurons in the hypothalamus. Surprisingly, Shah's team found that many of these genes also show sex differences in the amygdala, a part of the brain important for emotions.

In further studies, the researchers examined the effects of a subset of these individual genes. Mice missing only one of these 16 genes seemed to behave normally. But upon closer observation, these mice showed significant differences in sex-specific behaviors. For instance, Shah explained, females mutant for one gene took longer to return their pups to the nest and to fight off intruders. "They still take care of their pups, but less effectively," he said.

In other experiments, deletion of a single gene produced females that were two-fold less receptive to mating with males. Similarly, males mutant for another gene were less interested in females. Together these results mean that sex-specific behaviors can be controlled in modular fashion, such that the loss of any one gene leads to subtle but potentially important changes.

"At the superficial level, the mice appear normal, but this is pretty significant variation in behavior," Shah said. It suggests that variation in such genes might explain not just differences between the sexes, but also differences in behaviors within one sex or the other – why some male mice are more aggressive than other males or some females more attentive to their offspring than other females.

The researchers don't yet know exactly how these differences in gene expression lead to those differences in behavior, although Shah says some of the genes are known to be involved in sending or receiving neural messages in the brain. It also remains to be seen how the male and female gene expression programs might be influenced by the animals' social interactions and experiences.

There is still a lot to learn about what makes males and females tick. "This gene list of sex differences in the brain is probably just a small subset of what we will eventually unearth," Shah said.

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Cell Press: http://www.cellpress.com