From an evolutionary point of view, no physiological functions are as adaptive as those which ensure successful reproduction. In most animals, the constellation of behaviors that promote copulation and impregnation are vital to survival of a species. The male sex hormone testosterone (T) is essential for the expression of male sexual motivation and performance. Neural tissues metabolize T into estradiol (E2) by the cytochrome P450 aromatase (ARO). Numerous observations suggest that both T and E2 synergize to regulate sexual performance. Much remains to learned about the specific cellular pathways by which steroids act in the brain. Our preliminary results demonstrate that E2 exerts novel short-latency stimulatory effects on the motivational aspects of male sexual behavior. These data suggest that T-derived E2 could mediate male sexual activity through "non-classical", possibly non-transcriptional mechanisms in the brain. This novel hypothesis has never been tested before although there is substantial evidence that E2 is capable of exerting rapid effects on other aspects of the brain function. Thus, we will use stereotaxic drug administration and standard tests of male sexual behavior to systematically test a new model of the cellular mechanism underlying estrogenic control of male sexual behavior and determine the effect of in situ aromatization on sexual motivation. These studies are valuable because they will advance our understanding of the endocrine regulation of neural function in adult mammals.
