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 N 末端结构域的功能尚不完全清楚，并且似乎可以调节转录。由于其强亲水性，类固醇激素受体的抗体通常针对 N 末端区域。在卵巢切除的大鼠中，雌激素受体免疫反应性位于神经元的细胞核中，而不是位于细胞质或非神经元细胞（神经胶质细胞、内皮细胞和室管膜细胞）中。雌性大鼠的内侧视前区比雄性大鼠含有更多含有雌激素受体免疫反应性的神经元。在视前区的前腹侧室周核（AVPN-POA）中，女性雌激素受体免疫反应性神经元的数量比男性高几倍。对切除卵巢的大鼠进行雌激素治疗会减少雌性 AVPN-POA 中雌激素受体免疫反应性神经元的数量。研究发现，延伸轴突和树突的神经元含有雌激素受体。轴突或树突是否特别受到性腺类固醇的影响仍然存在争议，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。使用针对大鼠肝脏糖皮质激素受体的抗体进行的免疫组织化学研究表明，大脑中糖皮质激素受体免疫反应性的总体强度在围产期最高，在出生后第 12 天左右降至低强度，此后在大多数大脑区域再次逐渐增加至中等染色。新生儿期地塞米松治疗可诱导齿状回颗粒细胞凋亡变化。这表明肾上腺类固醇通过一种尚未确定的机制对细胞的产生产生间接影响。