Kelce W R, Ganjam V K, Rudeen P K
Department of Veterinary Biomedical Sciences, University of Missouri-Columbia 65211.
J Steroid Biochem. 1990 Jan;35(1):103-6. doi: 10.1016/0022-4731(90)90152-i.
The local formation of the testosterone metabolites 5 alpha-dihydrotestosterone and 17 beta-estradiol within the hypothalamic-preoptic area (HPOA) is essential for the normal sexual differentiation of the male central nervous system (CNS) during a perinatal critical period in the rat. Testosterone, the substrate for these reactions, is derived primarily from synthesis within the fetal testis. Fetal alcohol exposure (FAE) during this critical period profoundly affects fetal testicular steroidogenesis as well as the sexual differentiation of the CNS. The present study was conducted to determine whether FAE directly affects the local metabolism of androgens within the developing CNS or whether reduced androgen substrate, via a testicular lesion, is a more likely explanation for the known effects of FAE on the CNS. The enzymatic activities of 5 alpha-reductase and aromatase were simultaneously quantitated in the newborn rat HPOA following FAE. Neither the enzymatic activity of 5 alpha-reductase, aromatase nor their ratio were significantly influenced (P greater than 0.05) by FAE with respect to controls. FAE apparently does not alter the disposition of the androgens within the newborn rat HPOA. These results support the hypothesis that FAE alters the sexual differentiation of the CNS through inhibition of androgen biosynthesis at the level of the perinatal rat testis.
在下丘脑视前区（HPOA）局部形成睾酮代谢产物5α-双氢睾酮和17β-雌二醇，对于大鼠围产期关键期雄性中枢神经系统（CNS）的正常性分化至关重要。睾酮作为这些反应的底物，主要来源于胎儿睾丸内的合成。在此关键期的胎儿酒精暴露（FAE）会深刻影响胎儿睾丸的类固醇生成以及CNS的性分化。本研究旨在确定FAE是否直接影响发育中CNS内雄激素的局部代谢，或者通过睾丸损伤导致雄激素底物减少，是否更有可能解释FAE对CNS的已知影响。在FAE后，对新生大鼠HPOA中5α-还原酶和芳香化酶的酶活性进行了同时定量。与对照组相比，FAE对5α-还原酶、芳香化酶的酶活性及其比值均无显著影响（P>0.05）。FAE显然不会改变新生大鼠HPOA内雄激素的分布。这些结果支持了以下假设：FAE通过抑制围产期大鼠睾丸水平的雄激素生物合成来改变CNS的性分化。
