Connolly P B, Choate J V, Resko J A
Department of Physiology, School of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Neuroendocrinology. 1994 Mar;59(3):271-6. doi: 10.1159/000126668.
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 androgen receptors (AR) in the developing rhesus monkey brain, but did not present data concerning their capacity for activation. To achieve this end, we analyzed the AR content in brains from intact and gonadectomized rhesus monkey fetuses at approximately 125 days of gestation, 2 h after injection of either 500 micrograms dihydrotestosterone (DHT) or vehicle directly into the fetus. After treatment, plasma DHT concentrations increased five-fold in the fetal circulation. In gonad-intact fetuses, cytosolic AR decreased in preoptic area, medial basal hypothalamus, and septum following DHT treatment. No significant effect of DHT treatment on nuclear AR was seen. In contrast, the increased level of DHT in the maternal circulation decreased cytosolic AR and increased nuclear AR of the maternal myometrium. In gonadectomized fetuses, DHT treatment decreased cytosolic AR as it did in the intact group. In contrast, a significant increase in nuclear AR was seen in preoptic area, medial basal hypothalamus, and tegmentum of these fetuses. Thus AR in fetal rhesus brain can be activated by DHT when the gonads are removed, but not in the intact fetuses. These data suggest that AR in the developing nervous system of rhesus macaques can be activated by exogenous androgen and hence are probably functional.
胎儿睾丸分泌的睾酮在特定的产前关键期使非人灵长类动物的大脑男性化并抑制其女性化特征。我们之前已证实在发育中的恒河猴大脑中存在高亲和力的特异性雄激素受体（AR），但未提供有关其激活能力的数据。为了实现这一目标，我们分析了妊娠约125天时完整和性腺切除的恒河猴胎儿大脑中的AR含量，在直接向胎儿注射500微克双氢睾酮（DHT）或溶剂2小时后进行分析。治疗后，胎儿循环中的血浆DHT浓度增加了五倍。在性腺完整的胎儿中，DHT治疗后视前区、内侧基底下丘脑和隔区的胞质AR减少。未观察到DHT治疗对核AR有显著影响。相比之下，母体循环中DHT水平的升高降低了母体子宫肌层的胞质AR并增加了核AR。在性腺切除的胎儿中，DHT治疗与完整组一样降低了胞质AR。相反，在这些胎儿的视前区、内侧基底下丘脑和被盖中观察到核AR显著增加。因此，当性腺被切除时，恒河猴胎儿大脑中的AR可被DHT激活，但在完整胎儿中则不然。这些数据表明，恒河猴发育中的神经系统中的AR可被外源性雄激素激活，因此可能具有功能。
