In previous years, we investigated the steroid hormone milieu in which nonhuman primate fetuses develop. Subsequently, we provided evidence that long-loop negative feedback between the fetal gonads and the pituitary gland is established in fetal life and that dihydrotestosterone (DHT) can be a component of the feedback loop. In this grant application, we propose to continue this work by concentrating on androgen processing by neural tissue, a presumed site of androgen action in sexual differentiation. Two facets of the processing will be studied. First, we will investigate the distribution of 5Alpha-R reductase (5Alpha-R) activity throughout the central nervous system (CNS) and compare features of this activity in males and females. Once the loci for this activity is known, we will study its ontogeny and control, and will attempt to """"""""pinpoint"""""""" 5Alpha-R activity in particular brain nuclei. Comparisons will be made between fetal rhesus macaques and guinea pigs, another long-gestation mammal, for which similar data are not yet availabe. The second major thrust of this work will be to establish the loci that contain androgen receptors in both fetal monkeys and fetal guinea pigs. Previous observations in rats suggest that measurements of brain androgen receptors provide markers for the onset of the """"""""critical period"""""""" for sexual differentiation. We plan to study the ontogeny of brain androgen receptors in fetal monkeys and guinea pigs with the intention of obtaining new information about the onset of androgen-dependent developmental periods. The completed experiments will provide important new information about cellular events for androgen processing by neural tissue at the time of sexual differentiation.
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