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Steroid receptors-multiforms and their significance on brain differentiation

多种形式的类固醇受体及其对大脑分化的意义

基本信息

批准号：
07458257
负责人：
KAWATA Mitsuhiro
金额：
$ 1.09万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

The function of the N-terminal domain of steroid hormone receptors is not fully understood, and appears to modulate transcription. Antibodies to steroid hormone receptors are generally directed against the N-terminal region because of its strong hydrophilicity. Estrogen receptor immunoreactivity was localized in the nuclei of neurons, not in the cytoplasm or non-neuronal cells (glia, endothelium, and ependymal cells) in the ovariectomized rat. The medial preoptic area of female rat contains more neurons containing the estrogen receptor immunoreactivity than male. In the anteroventral periventricular nucleus of the preoptic area (AVPN-POA), estrogen receptor immunoreactive neurons are present in numbers several times higher in females than males. Estrogen treatment of ovariectomized rats reduces the number of estrogen receptor-immunoreactive neurons in the AVPN-POA of females. It was found that neurons extending their axons and dendrites contain estrogen receptors. Whether axons or dendrites are specifically affected by gonadal steroids is still controversial, because hypothalamic neurons have no distinctive polarity such as neurons in the hippocampus. The number of cells containing glucocorticoid receptor immunoreactivity and the intensity of immunoreactivity per cell showed age-related variations. Immunohistochemical studies using an antibody against rat liver glucocorticoid receptor showed that overall intensity of glucocorticoid receptor immunoreactivity in the brain was the highest perinatally, decreased to a low intensity around postnatal day 12, and thereafter increased gradually again to moderate staining in most brain areas. Dexamethasone treatment at the neonatal period induces apoptotic changes of granule cells in the dentate gyrus. This suggests that adrenal steroids have an indirect influence on cell birth through an as yet unidentified mechanism.

类固醇激素受体的N-末端结构域的功能尚未完全了解，并且似乎调节转录。类固醇激素受体的抗体通常针对N-末端区域，因为其具有强亲水性。雌激素受体免疫反应定位于神经元的细胞核，而不是在细胞质或非神经元细胞（胶质细胞，内皮细胞，室管膜细胞）在卵巢切除大鼠。雌鼠内侧视前区雌激素受体阳性神经元数目多于雄鼠。在视前区的前腹侧室周核（AVN-POA），雌激素受体免疫反应阳性神经元的数量在女性比男性高几倍。雌激素治疗卵巢切除大鼠减少雌激素受体免疫反应神经元的数量在AVPN-POA的女性。研究发现，延伸轴突和树突的神经元含有雌激素受体。轴突或树突是否受到性腺类固醇的特异性影响仍然存在争议，因为下丘脑神经元没有像海马神经元那样独特的极性。含有糖皮质激素受体免疫反应性的细胞数量和每个细胞的免疫反应性强度显示出与年龄相关的变化。免疫组织化学研究表明，使用抗大鼠肝脏糖皮质激素受体的抗体，糖皮质激素受体的免疫反应性在大脑中的整体强度是最高的围产期，出生后12天左右降低到低强度，此后逐渐增加再次中度染色在大多数大脑区域。新生儿期地塞米松治疗诱导齿状回颗粒细胞凋亡的变化。这表明肾上腺类固醇通过一种尚未确定的机制对细胞出生产生间接影响。