Neural Steroid Hormone Receptors: Subcellular Analysis

卵巢类固醇激素雌二醇通过大脑的活动调节生理和行为。雌二醇与特定神经脑区域内目标神经元中的细胞内蛋白受体结合。然后这些类固醇受体复合物与细胞核中的受体位点结合，改变基因表达（即诱导RNA和蛋白质合成）。人们认为，由这种类固醇受体相互作用引起的蛋白质的增加和减少是激素作用的主要机制。虽然雌二醇诱导的许多生理、形态和行为效应可以用这种机制来解释，但最近的免疫细胞化学研究已经在目标神经元的核外区域发现了类固醇激素受体。这有力地表明激素也通过非基因组过程起作用。布劳斯坦博士将在神经元内确定雌二醇可能起作用的其他位置。由于在光镜水平上不同的细胞定位不能很容易地识别，他将开发一种电子显微镜下的超微结构免疫细胞化学技术。利用这项技术，布劳斯坦博士将确定与类固醇受体相关的核外细胞器。这些解剖研究将大大提高我们对这种激素作用的细胞机制的理解。许多研究表明雌二醇与各种癌症的发生有关。更好地了解其作用机制可能最终导致改善这些危及生命的雌激素相关疾病的治疗和可能的治愈。

The ovarian steroid hormone, estradiol, regulates physiology and behavior by actions in the brain. Estradiol binds to intracellular protein receptors found in target neurons within the specific neural brain regions. These steroid-receptor complexes then bind to acceptor sites in the nucleus to alter gene expression (i.e. induction of RNA and protein synthesis). It is the believed that the increase and decrease of proteins resulting from this steroid-receptor interaction is the primary mechanism of action of the hormone. While many of the physiological, morphological and behavioral effects induced by estradiol can be accounted for by this mechanism, recent immunocytochemical studies have identified steroid hormone receptors in the extranuclear regions of the target neurons. This strongly suggests that the hormone also acts through a nongenomic process. Dr. Blaustein will identify other possible sites within neurons at which estradiol acts. Since at the light microscopic level distinct cellular localization can not be readily identified, he will develop an electron microscopic, ultrastructural immunocytochemical technique. Using this technique, Dr. Blaustein will determine the extranuclear organelles with which the steroid receptors are associated. These anatomical studies will significantly enhance our understanding of the cellular mechanisms of action of this hormone. A number of studies have linked estradiol with the occurrence of various types of cancers. A better understanding of the mechanisms of action could eventually lead to improved treatments and possible cures for these life threatening estrogen-related diseases.