97-28579 OGAWA It is well known that that the activation of androgen and estrogen receptors is important for the regulation of sex-specific brain organization and behavior. It is also well accepted that testosterone plays a major role in the expression of aggressive behavior in all animals. There is a positive correlation between plasma testosterone levels and aggressive behaviors. Thus, it was surprising to find that knockout mice that lack the alpha estrogen receptor rarely show male-typical aggressive behavior despite the fact that they have normal levels of testosterone. Moreover, testosterone restored aggressive behavior in wildtype gonadectomized mice but not in these estrogen receptor knockout mice. In contrast, females mice that lack the alpha estrogen receptor had enhanced levels of aggressive behavior. Dr. Ogawa will investigate why gene disruption of the alpha-form of the estrogen receptor greatly modifies the expression of aggressive behaviors in these male and female mice. The results from these studies will provide novel insights into the normal mechanisms by which estrogen mediates neural regulation of sexually-dimorphic behaviors. The use of genetic mutations involving steroid family, such as the Tfm mutation and this new alpha estrogen receptor knockout has been invaluable for elucidating the molecular basis of sexual dimorphism as well as identifying the hormones mediating sexual differentiation of the brain and behavior.
