EFFECTS OF EXOGENOUS ANDROGEN ON BRAIN ANDROGEN RECEPTORS OF THE FETAL RHESUS-MONKEY

Testosterone secreted by the fetal testes masculinizes and defeminizes the nonhuman primate brain during a defined prenatal critical period. We previously demonstrated the presence of high-affinity, specific an drogen receptors (AR) in the developing rhesus monkey brain, but did n ot present data concerning their capacity for activation. To achieve t his end, we analyzed the AR content in brains from intact and gonadect omized rhesus monkey fetuses at approximately 125 days of gestation, 2 h after injection of either 500 mu g dihydrotestosterone (DHT) or veh icle directly into the fetus. After treatment, plasma DHT concentratio ns increased five-fold in the fetal circulation. In gonad-intact fetus es, cytosolic AR decreased in preoptic area, medial basal hypothalamus , and septum following DHT treatment. No significant effect of DHT tre atment on nuclear AR was seen. In contrast, the increased level of DHT in the maternal circulation decreased cytosolic AR and increased nucl ear AR of the maternal myometrium. In gonadectomized fetuses, DHT trea tment decreased cytosolic AR as it did in the intact group. In contras t, a significant increase in nuclear AR was seen in preoptic area, med ial basal hypothalamus, and tegmentum of these fetuses. Thus AR in fet al rhesus brain can be activated by DHT when the gonads are removed, b ut not in the intact fetuses. These data suggest that AR in the develo ping nervous system of rhesus macaques can be activated by exogenous a ndrogen and hence are probably functional.