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

在醛固定的大鼠和猴子的脑中，神经元芳香酶的存在已被免疫组织化学检测到。最显著的芳香酶免疫反应(AROM-I)神经元存在于两种动物的内侧视前杏仁核神经元弧(mPOAM弧)。这些区域一直被认为是生殖功能的中心，雄性的大小大于雌性，证实了脑内雌激素的生物合成对哺乳动物生殖神经底物和功能的发育是必不可少的。它们在大鼠胚胎15岁时出现，在EL 8-P2之间达到染色强度的峰值，并在围产期后逐渐减弱。在mPOAM弧区，男性的表达在数量和免疫反应性方面明显高于女性，尤其是在幼年到成年阶段之后。AROM-I神经元也已被澄清，显示出α-雌激素和雄激素受体(ESR和ANR)的性别二型性表达。新生儿mPOAM Arc I…中血沉的表达更多的S在女性中已经比男性更突出，而ANR在男性中比女性更突出。在青春期到成年期，随着雌性ESR或雄性ANR表达的增加，性二型性表达进一步增强。新生大鼠去势后，在mPOAM弧区的AROM、ESR和ANR等指标上，雄鼠由雄鼠变为雌鼠。给予5α-二氢睾酮后，新生去势雄性大鼠脑内AROM和ANR的表达明显增加，ESR略有增加，而17β-雌二醇组AROM和ANR的表达略有增加，EsR的表达明显降低，提示只有睾酮才能恢复新生去势大鼠mPOAM弧区AROM和ANR的表达，显著降低ESR的表达。因此，一些睾酮被认为实际上是芳香化成雌二醇并下调ESR，而另一些没有芳构化的则可以直接作用于mPOAM弧中的ANR。一个完整的男性可能不仅需要通过上调ANR来增强ANR刺激的阳性化，而且还需要通过降低下缘弧内ESR的下调来减少ESR刺激的去雌化。较少

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