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

在醛固定的大鼠和猴脑中，神经元芳香酶的存在已被确定，最显着的芳香酶免疫反应性 (AROM-I) 神经元存在于两种动物的内侧视前杏仁神经元弧 (mPOAM 弧) 中。被认为是生殖功能的中心，并且男性的尺寸大于女性，证实颅内雌激素生物合成对于发育至关重要它们在大鼠中出现于 E15，在 El 8-P2 之间达到染色强度峰值，并在围产期后减弱，mPOAM 弧中的表达在数量和免疫反应性方面明显更为突出。与女性相比，尤其是在年轻到成年阶段之后，AROM-I 神经元也被证实显示出 α-雌激素和雄激素受体（EsR 和）的性别二态性表达。在新生儿中，mPOAM 弧中 EsR 的表达在女性中比在男性中更突出，而 AnR 在男性中比在女性中更突出。随着青春期雌性 EsR 或雄性 AnR 表达的增加，雄性大鼠的新生去势发现 AROM、EsR 和 AnR 的表达从雄性模式变为雌性模式。 mPOAM弧中的AnR强烈增加AROM和AnR的表达并轻微增加EsR，而17β-雌二醇轻微增加AROM和AnR的表达并降低EsR的表达。睾酮增加AROM的表达。和 AnR，并强烈降低 mPOAM 弧中 EsR 的表达，表明只有睾酮才能恢复新生儿雄性模式的表达因此，一些睾酮被认为实际上被芳构化为雌二醇并下调 EsR，而另一些则保留芳构化可以直接作用于 mPOAM 弧中的 AnR 一个完整的雄性可能不仅需要通过增强 AnR 来实现男性化。 -通过上调 AnR 进行刺激，但也通过下调 Iimbic 弧中的 EsR 来减少 EsR 刺激，从而实现去女性化。