The purpose of this application is to generate new information about the localization of brain aromatase activity (AA) and its control by androgen in nonhuman primates and laboratory rodents. In the previous grant period we described the distribution of AA in monkey and rat brains and provided evidence for androgen dependent and independent control mechanisms. We demonstrated that AA and AR are heterogeneously distributed in discrete regions of the brain and that they colocalize in the same areas, thus providing a cellular component for androgens to exert their effects. Aromatase activity in the brain decreased after castration and was restored to normal levels following androgen treatment. In this renewal application we hope to extend the work begun in the first grant period to include experiments that probe the cellular events that underlie the biological function of AA in the mammalian brain. We hypothesize that the state of refractoriness to the feedback action of T on gonadotropin secretion that we observed in rhesus monkeys after castration occurs because of estrogen deficiency. Our experiments will address the physiological role of in situ estrogen production in gonadotropin control in nonhuman primates and rodents and in rodent sexual behavior. Using molecular probes for aromatase P-450 and AR that are now available to use we hope to use the tools of molecular biology to investigate the distribution and control of mRNA and AR in male rats and rhesus monkeys. In this way we hope to elucidate some of the steps that constitute the """"""""gray area"""""""" between androgen binding to its receptor and the induction of AA. Finally, we suspect that a complex series of interactions exists between the in situ production of estrogen within the nervous system, the synthesis and activation of the AR and the inductive effects of androgen on AA. the proposed experiment address some of these issues.
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