In this proposal we plan to study endocrine factors that control aromatization in the central nervous system (CNS). Preliminary data suggest that brain aromatization in rodents is controlled by testosterone. Now we will localize this activity to specific regions and nuclei of the CNS, study specificity of hormone action and thresholds for its induction by steroid hormones. Further analysis of aromatase activity (AA) will be obtained in proposed studies that will investigate the necessity of androgen receptors, for the inductive action of androgen on brain AA. We postulate that AA is controlled differently in different parts of the CNS and that different species of the enzyme complex are distributed regionally within the brain. Experiments are proposed that will investigate these possibilities. Some studies performed first on rodents will be expanded to include nonhuman primates (Macaca mulatta). In the primate studies we will localize aromatase within the CNS and determine the effects of castration and androgen replacement on its activity. We wish to know whether AA and GnRH quantified by RIA are localized within the same brain regions. We have developed a new antisera to GnRH that appears promising for these studies. A developmental study is proposed in which placental aromatase will be solubilized and purified by column chromatography. Antibodies will be produced with the intent of performing immunocytochemistry at some future date. The data that will be generated in rodents will be important additions to the existing literature (which is quite small) on endocrine factors that control aromatization in the brain. The primate studies are important because: a) They represent the first real attempt to identify control mechanisms for aromatase and their regional distribution within the brain of non-human primates.
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