The purpose of this application is to generate new information about the organizing actions of androgen at the cellular level on the brain of two long gestation mammals, the guinea pig and the rhesus monkey. Based on preliminary data, experiments are proposed which will carefully plot changes in the ontogeny of cytosolic androgen receptors (ARc) in the cortex and hypothalamus of these species at critical times in fetal development and relate these changes to the effects of androgen on sexual responsiveness and the capacity of males to release gonadotropins in a cyclic manner. Attempts will be made to systematically evaluate the technique for quantifying nuclear androgen receptors (ARn) since they can not be measured in fetal tissues by conventional means. The actions of tissue proteases on ARn destruction will be studied as well as possible localization within the nuclear matrix. Studies are proposed in which the role of brain aromatization in sexual differentiation will be ascertained by the use of aromatase inhibitors during pregnancy. In addition molecular probes have been obtained to study the ontogeny of mRNA for aromatase P-450 in the rhesus monkey fetus. Likewise, the capacity of exogenous testosterone to androgenize the cyclic centers that control gonadotropin release in the fetal guinea pig will be evaluated. These studies will provide new information on cellular events that mediate hormonal control of brain development.
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