Gender behaviors directly manipulated

Uncovering the individual genes that are directly influenced by testosterone and estrogen has allowed University of California, San Francisco scientists to manipulate individual behaviors in mice, such as sex drive, desire to pick fights, or willingness to spend extra time caring for their young.

Explaining his work in the journal Cell, researcher Nirao Shah said that each gene his team identified regulates a few components of a behavior without affecting other aspects of male and female behavior.

Scientists have long known that hormones exert a profound influence over male and female biology. They control the gender of an embryo and promote gender-specific characteristics, such as facial hair in men and breasts in women.

While the connection between sex hormones and behavior has been recognized for years, scientists have only recently made significant headway in understanding how sex hormones ultimately influence gene expression in the brain. About six years ago, Shah and his colleagues set out to find such genes and to analyze gender differences in gene expression in the hypothalamus.

The researchers found 16 genes that were expressed differently between males and females in the hypothalamus and showed that such differences were regulated by sex hormones. But in identifying these 16 genes, Shah also discovered he could tease apart classic, male and female hormone-driven behaviors into individual elements – each governed by its own genes.

Shah said the situation is analogous to the way a house draws its power from the grid. A sex hormone is similar to the main breaker that connects the house to the utility pole and regulates electricity to the entire house. Individual genes influenced by sex hormones are like the light switches in each room, making it possible to turn the lights on in the kitchen while leaving the bedroom dark.

Much like a main electrical box with many breaker switches, male and female behaviors are actually made up of many behaviors, like sex drive or an inclination to fight. Shah and his colleagues showed that they could selectively knock out some male behaviors so that males continued to fight and mark territory normally but altered their mating routine with females. Likewise they could modulate female mouse behaviors to make them maintain active interest in sex but spend less time caring for their young, or vice versa.

“Other components of male and females behaviors appeared unchanged,” Shah noted. “The implications of this simple observation that a complex human behavior may be composed of numerous genetically controlled elements are both intriguing and daunting.” He believes that there are many additional genes that will be discovered to be sex hormone regulated that, in turn, control other components of male or female behaviors.

How genetic differences in our brains account for our behaviors may also be a starting point for understanding how to better address mental illness and neurodegenerative conditions in which gender skew exists. For example, autism is four times more common in males than in females.

“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,” said Shah. “We won’t immediately find all the answers to these disorders based on this research alone, but in the future, it might indeed help to identify more informed ways of treating such conditions.”

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Source: University of California, San Francisco

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