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Genes Affect Sex Differences in Behavior

Men and women can seem like they’re from different planets sometimes. Hormones help drive those differences. A new study shows how genes pass on the message.

Hormones are the body's signaling molecules. They affect many aspects of development and biology. Researchers have long known that the sex hormones, such as estrogen and testosterone, drive certain differences in behavior between men and women. For example, estrogen prompts maternal behavior, while testosterone drives aggressive, territorial behavior in males. How these hormones exert their effects on a molecular level, however, isn't well understood.

A team of scientists led by Dr. Nirao Shah at the University of California, San Francisco, suspected that sex hormones ultimately influence gene expression in the brain. They used DNA microarrays to analyze gene expression across the mouse brain. They particularly focused on the hypothalamus, a region known to be involved with hormone sensing. Their study was funded by NIH's National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH) along with several other sources.

In the February 3, 2012, issue of Cell, the team reported finding 16 genes that were expressed differently between the brains of male and female mice. A closer look revealed that these sex differences in gene expression weren’t limited to the hypothalamus. They were also found in the amygdala, a region implicated in processing emotions.

To see how these genes can affect mouse behavior, the scientists studied mice with disruptions in each of 4 selected genes: Brs3, Cckar, Irs4 and Sytl4. They found that mice with each single-gene disruption showed unique differences in certain sex-specific behaviors. For example, females with Irs4 disruptions were less effective at maternal care. Females without Cckar were less receptive to male mating attempts. Males without Brs3 were quicker to mate or fight, whereas males lacking Sytl4 sniffed females less but increased other aspects of male mating behavior. Strikingly, mice mutant for each of these genes appeared normal for other sex-specific behaviors.

“It's as if you can deconstruct a social behavior into genetic components,” Shah says. "Each gene regulates a few components of a behavior without affecting other aspects of male and female behavior.”

In addition to illuminating the role of these genes in gender-related behavior, these findings could lead to insights into mental illness and neurological conditions that differ between the sexes. Autism spectrum disorders, for example, are more common in boys than girls.

“Some of the genes we have identified in our study have indeed been implicated in various human disorders that are found in sex-skewed ratios,” Shah says. “We won't immediately find all the answers to these disorders based on this research alone, but in the future, it might help to identify more informed ways of treating such conditions.”

These results also suggest that other complex behaviors might be similarly constructed by gene networks. Of course, genes aren't the only things that drive how people behave. But this research shows that genes may play an important role in complex human behavior.

—by Harrison Wein, Ph.D.