Matthews Jason, Gustafsson Jan-Ake
Department of Biosciences at Novum, Karolinska Institutet, S-141 57 Huddinge Sweden.
Mol Interv. 2003 Aug;3(5):281-92. doi: 10.1124/mi.3.5.281.
The biological actions of estrogens are mediated by estrogen binding to one of two specific estrogen receptors (ERs) ERalpha and ERbeta, which belong to the nuclear receptor superfamily, a family of ligand-regulated transcription factors. ERalpha and ERbeta are products of different genes and exhibit tissue- and cell-type specific expression. The characterization of mice lacking ERalpha, or ERbeta, or both has revealed that both receptor subtypes have overlapping but also unique roles in estrogen-dependent action in vivo. Additionally, ERalpha and ERbeta have different transcriptional activities in certain ligand, cell-type, and promoter contexts. Both receptors, however, are coexpressed in a number of tissues and form functional heterodimers. The biological roles of ERalpha /beta heterodimers in the presence of each respective homodimer are unknown. When coexpressed, ERbeta exhibits an inhibitory action on ERalpha -mediated gene expression and in many instances opposes the actions of ERalpha. A number of ERalpha and ERbeta isoforms have also been described, many of which alter estrogen-mediated gene expression. Uncovering the molecular mechanisms regulating the expression of both ERs, and how ERalpha and ERbeta directly or indirectly affect each other's function are paramount to understanding the cellular and biological events of estrogen-mediated gene regulation in normal and diseased tissues.
雌激素的生物学作用是通过雌激素与两种特定雌激素受体（ERs）之一结合来介导的，即ERα和ERβ，它们属于核受体超家族，这是一类配体调节的转录因子家族。ERα和ERβ是不同基因的产物，表现出组织和细胞类型特异性表达。对缺乏ERα、ERβ或两者皆缺的小鼠的特征研究表明，这两种受体亚型在体内雌激素依赖性作用中具有重叠但也独特的作用。此外，在某些配体、细胞类型和启动子环境中，ERα和ERβ具有不同的转录活性。然而，两种受体在许多组织中共同表达并形成功能性异二聚体。在各自同二聚体存在的情况下，ERα/β异二聚体的生物学作用尚不清楚。当共同表达时，ERβ对ERα介导的基因表达表现出抑制作用，并且在许多情况下与ERα的作用相反。还描述了许多ERα和ERβ的亚型，其中许多改变了雌激素介导的基因表达。揭示调节两种ERs表达的分子机制，以及ERα和ERβ如何直接或间接影响彼此的功能，对于理解正常和患病组织中雌激素介导的基因调控的细胞和生物学事件至关重要。
