Credit: Monika Wisniewska

Sexual dimorphism is the presence of different behaviors and characteristics in males versus females. Its development relies on an intricate interplay of genetic, chromosomal and hormonal factors, particularly during certain stages of development. In mammals, sexual dimorphism is thought to result from exposure to sex hormones during the perinatal stage of development. In male rats, an increase in testosterone expression occurs during this period, resulting in male-specific brain circuitry and the establishment of certain male-specific characteristics. Now, a new study has identified the neural pathways underlying territorial behavior in male mice and, furthermore, shown that these pathways are controlled by estrogen.

Researchers had known that estrogen was involved in sexual dimorphism, but not how. The new work, done by Nirao Shah and colleagues at the University of California, San Francisco and Fujita Health University (Toyoake, Japan), elucidates a mechanism of action for estrogen in regulating male territorial behavior. They found that male mice had a greater number of neurons that express an enzyme called aromatase in specific areas of the brain known to be involved in sexual and aggressive behaviors (Cell 139, 61–72; 2009). These aromatase-expressing neurons also established a unique circuitry in male brains. Aromatase converts testosterone into estrogen, which is required for the unique circuitry.

When Shah's group exposed female pups to estrogen, the females began engaging in aggressive and territorial behaviors typically found in males, and the aromatase neurons in their brains took on the 'male' circuitry. Exposure to estrogen did not affect sexual behavior in the females, however. “This really changes the way we view male and female behaviors,” said Shah. “What we previously looked upon as a single unit of gender-related behavior, we now see as a collection of separate behaviors controlled at least in part by distinct neural pathways.”

The new results add to the body of evidence that estrogen signaling has a key role in the expression of male aggressive behavior and the development of the neural pathways that underlie it. Neural pathways in the brain are largely conserved between mice and humans, and hormone-induced dimorphism may also be conserved. But much more research is needed on the development of sex-specific neural pathways; many other factors, including genetics and socialization, contribute to sexual differentiation.

Shah's approach could also be used in studies attempting to link other specific behaviors with their underlying neural pathways.