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

神经元芳香酶的存在已在醛固定的大鼠和猴子大脑中进行免疫组织化学确定。两种动物的内侧前 - 杏仁糖神经元（MPOAM弧）中，最引人注目的芳香酶 - 免疫反应（AROM-I）神经元存在。这些区域被认为是生殖功能的中心，而男性的大小比女性大小，证实颅内雌激素生物合成对于生殖神经元的发展至关重要，为α-雌激素和雄激素受体提供了性二态表达。（ESR和ANR）。在新生儿中，ESR在mpoam弧中的表达在女性中比男性更为突出，而在男性中，ANR比男性更为突出。在年轻人到成年的阶段，根据青少年期间女性或男性ANR的ESR表达的增加，性二态表达进一步增强。发现雄性大鼠的新生儿cast割将男性的模式转换为雌性在MPOAM弧中的Arom，ESR和ANR方面的模式。 5α-二氢睾丸激素的施用强烈增加了芳香和ANR的表达并稍微增加ESR，而17beta-雌二醇稍微增加了AROM和ANR的表达，并且强烈降低了ESR的表达。Testosteron.testosteron.testosteronsof AROM和ANR的表达仅会降低ESR的表达，并且在ESR中的表达仅恢复了ESR的表达，以至于MM的表达能够恢复MMA，ARC的表达是ARC AR的表达，ARC的表达是ARC AR的表达。新生儿cast割的雄性大鼠的模式。这是某些睾丸激素实际上被认为是芳香化的雌二醇并下调ESR，而另一些睾丸激素可以直接作用于MPOAM ARC中的ANR。一个完整的男性不仅需要通过上调ANR来增强ANR刺激，而且还需要通过减少ESR刺激通过IIMBIC ARC中ESR的下调来进行定义。较少的