Mechanism of brain sexual differentiation by regulation of aromatase and sex-steroid receptors.

用免疫组织化学方法测定了醛固定大鼠和猴脑中神经元芳香化酶的存在。在这两种动物中，最显著的芳香酶免疫反应（芳香-i）神经元存在于内侧视前杏仁核神经元弧（mPOAM弧）中。这些区域被认为是生殖功能的中心，雄性比雌性更大，证实了颅内雌激素生物合成对哺乳动物生殖神经基质和功能的发育至关重要。它们在大鼠E15出现，在El 8-P2之间染色强度达到峰值，在围产期后逐渐减弱。在数量和免疫反应性方面，mPOAM弧线在男性中的表达明显比女性更突出，尤其是在青年到成年阶段。芳香- 1神经元也已被证实对α -雌激素和雄激素受体（EsR和AnR）表现出两性二态表达。在新生儿中，mPOAM中EsR的表达在女性中比男性更突出，而AnR在男性中比女性更突出。在青年到成年阶段，两性二态表达进一步增强，与青春期女性中EsR或男性中AnR的表达增加一致。研究发现，雄性大鼠在新生儿阉割后，其mPOAM曲线上的AROM、EsR和AnR均改变为雄性模式。5 α -二氢睾酮可使AROM和AnR表达明显升高，EsR略有升高；17 β -雌二醇可使AROM和AnR表达明显升高，EsR表达明显降低。睾酮能强烈增加AROM和AnR的表达，强烈降低mPOAM区EsR的表达，说明只有睾酮能恢复初生去势雄性大鼠的雄性模式表达。因此，一些睾酮被认为实际上是芳构化成雌二醇并下调EsR，而其他不芳构化的睾酮可以直接作用于mPOAM弧中的AnR。一个完整的雄性可能不仅需要通过AnR的上调来增强AnR刺激的男性化，还需要通过降低脑边弧EsR的下调来减少EsR刺激的去女性化。少

The presence of neuronal aromatase has been immunohistochemically determined in the aldehyde-fixed rat and monkey brains. The most striking aromatase-immunoreactive (AROM-I) neurons are present in the medial preoptico-amygdaloid neuronal arcs (mPOAM arcs) in both animals. The regions have been considered as centers of reproductive functions and larger in size in males than in females, confirming that intracranial estrogen-biosynthesis is essential to development of reproductive neural substrates and functions in mammals. They appear by E15 in the rat, reaching a peak in staining intensity between El 8-P2 and diminishing after the perinatal stage. Expression in the mPOAM arc are clearly more prominent in males in number and immunoreactivity than in females, especially after young-to-adult stages. The AROM-I neurons have also been clarified to show sexually dimorphic expression for both alpha-estrogen and androgen receptors (EsR and AnR). In neonates, expression of EsR in the mPOAM arc i … More s already more prominent in females than in males, whereas that of AnR is more prominent in males than in female. In young-to-adult stages, the sexually dimorphic expressions are further enhanced in accordance with increased expressions of EsR in females or AnR in males during adolescence. Neonatal castration in male rats was found to change the male's pattern to the female's one with respect to AROM, EsR and AnR in the mPOAM arc. Administration of 5alpha-dihydrotestosterone strongly increases the expressions of AROM and AnR and slightly increase EsR, while 17beta-estradiol slightly increases the expressions of AROM and AnR and strongly decreases the expression of EsR.Testosterone strongly increases the expressions of AROM and AnR, and strongly decreases the expression of EsR in the mPOAM arc, indicating that only testosterone can recovered expression of the male pattern in the neonatally castrated male rats. Thus, some testosterones are considered to be actually aromatized into estradiol and to down-regulate EsR, while others sparing aromatization can act directly on AnR in the mPOAM arc. A complete male probably requires not only masculinization by enhancement of an AnR-stimulation via the up-regulation of AnR but also defeminization by reduction of an EsR-stimulation via the down-regulation of EsR in the Iimbic arc. Less