What are little boys made of?

What makes a man behave like a man and a woman a woman? The answer may be partly in your genes. Researchers at the University of Virginia Health System have discovered a new twist on the role that estrogens play in the development of behavioral differences between males and females.

In laboratory tests on mice, the researchers found evidence that an estrogen receptor in the hypothalamus called ERb regulates defeminization, a process by which males lose the ability to display female-type behavior in adulthood. Defeminization is believed by many experts to be the main neurological process that differentiates males and females before birth. The discovery is detailed in the March 10 edition of the Proceedings of the National Academies of Sciences found at: www.pnas.org.

“Our hypothesis is that neonatal males are exposed to the steroid estradiol (a form of natural estrogen) produced by their testes. Estradiol binds to the estrogen receptor (ERb) and this acts to turn on, or turn off, other genes which sculpt the neural architecture required for adult function,” said the study’s main author, Emilie Rissman, PhD, a professor of biochemistry and molecular genetics at U.Va. and a specialist in the genetics of mammalian behavior. “We’d like to find out what the genes are, where precisely they reside in the brain, when in development this happens, and what the cellular targets are of these genes,” Rissman said. Interestingly, male fetuses are exposed to estrogen in their normal development and females are not because ovaries don’t fully develop until puberty.

This newly described role for ERb could be important in research on behavioral differences between men and women, Rissman said, such as in the areas of aggression, nurturing, and cognition. The discovery could also help scientists find out why some diseases target men and women differently, Rissman said, including depression, Alzheimer’s and multiple sclerosis to name just a few. Lupus, for instance, is nine times more prevalent in women than men. Depression is more likely to affect women as well. “The more we know about how these sex differences may be established in the brain and periphery, the more likely it is we will discover cures,” Rissman said.

Co-authors on this article with Rissman are Andrea E. Kudwa and Cristian Bodo, both graduate students in the U. Va neurosciences program and the discoverer of ERβ, Jan-Åke Gustafsson, of the Karolinska Institutet in Huddinge, Sweden.