雌激素受体亚型及其配体调节基因转录机制的研究

本文综述雌激素受体亚型（ERα和ERβ）的结构,功能,组织分布,生理作用及雌激素受体配体调节基因转录的机制,目的是深入系统地了解植物雌激素和选择性雌激素受体调节剂的作用路径及其组织特异性的发生机制,最终为提高雌激素类药物的选择性,优化以临床为基础的药物设计提供一条较为系统的思路。结果表明,ERα和ERβ对不同雌激素类化合物产生不同应答,配体的结构不同,调节基因转录的路径不同和募集的辅调节蛋白的不同是雌激素受体两种亚型组织特异性激活或抑制的主要原因。

Estrogen receptor subtypes and the regulatory effect of receptor ligand binding on gene transcription

This review introduces the structure, functions, tissue distribution, physiologic roles of estrogen receptor subtypes (ER alpha and ER beta) along with transcriptional activities of estrogen receptor ligands and the mechanism of the modulatory pathway and tissue specific property of selective estrogen receptor modulators (SERMs), and phytoestrogens. This article is to provide a systemic approach for increasing the selectivity of estrogenic drug and optimizing the clinically based strategy of drug design. Differences exist between ER alpha and ER beta in structure, function, tissue distribution, physiologic roles and response to ligands, as well as the regulating effect on gene transcription, which are mainly determined by different co-regulators they recruit respectively.