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

通过芳香酶和性类固醇受体调节的大脑性别分化机制。

基本信息

批准号：
08458262
负责人：
SHINODA Koh
金额：
$ 4.99万
依托单位：
Yamaguchi University (1998)Kinki University (1996-1997)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

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

神经元芳香化酶的存在已被电化学确定在固定的大鼠和猴脑。最引人注目的芳香化酶免疫反应（AROM-I）神经元存在于内侧视前杏仁核神经元弧（mPOAM弧）在这两种动物。这些区域被认为是生殖功能的中心，雄性的体积大于雌性，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。它们在大鼠中E15出现，在E18-P2之间达到染色强度的峰值，并且在围产期后减弱。mPOAM弧中的表达在雄性中在数量和免疫反应性方面明显比雌性更突出，特别是在哺乳动物至成年阶段之后。AROM-I神经元也已被阐明为显示α-雌激素和雄激素受体（EsR和AnR）的性二态表达。在新生儿中，EsR在mPOAM弧中的表达高于正常对照组。 ...更多信息 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。在胚胎发育至成年阶段，性二态表达进一步增强，与青春期雌性EsR或雄性AnR表达的增加一致。雄性大鼠去势后，mPOAM弧中AROM、EsR和AnR的模式由雄性变为雌性。给予5 α-双氢睾酮强烈增加AROM和AnR的表达，并轻微增加EsR，而17 β-雌二醇轻微增加AROM和AnR的表达，并强烈降低EsR的表达。表明只有睾酮才能恢复去势雄性大鼠的雄性模式表达。因此，一些睾酮被认为是实际芳构化成雌二醇和下调EsR，而其他保留芳构化可以直接作用于AnR在mPOAM弧。一个完整的男性可能不仅需要通过上调AnR来增强AnR刺激的雄性化，而且还需要通过下调边缘弧中的EsR来减少EsR刺激的去雌性化。少