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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n端结构域的功能尚不完全清楚，似乎是调节转录。类固醇激素受体的抗体通常是针对n端区域，因为它的亲水性很强。在去卵巢大鼠中，雌激素受体的免疫反应性局限于神经元核，而不局限于细胞质或非神经元细胞（胶质细胞、内皮细胞和室管膜细胞）。雌性大鼠内侧视前区含有较多的雌激素受体免疫反应性神经元。在视前区腹前侧脑室周围核（AVPN-POA）中，雌性雌激素受体免疫反应神经元的数量是雄性的数倍。去卵巢大鼠雌激素治疗可减少雌性AVPN-POA中雌激素受体免疫反应神经元的数量。研究发现，延伸轴突和树突的神经元含有雌激素受体。至于是轴突还是树突受到性腺类固醇的特异性影响，目前仍有争议，因为下丘脑神经元不像海马神经元那样具有明显的极性。具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表现出与年龄相关的变化。使用抗肝糖皮质激素受体抗体的免疫组化研究显示，大鼠大脑中糖皮质激素受体免疫反应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，随后在大部分脑区再次逐渐增加至中度染色。新生儿期地塞米松治疗诱导齿状回颗粒细胞凋亡改变。这表明肾上腺类固醇通过一种尚未确定的机制间接影响细胞生成。