Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Nat Rev Endocrinol. 2011 Aug 16;7(12):715-26. doi: 10.1038/nrendo.2011.122.
Estrogens mediate profound effects throughout the body and regulate physiological and pathological processes in both women and men. The low prevalence of many diseases in premenopausal women is attributed to the presence of 17β-estradiol, the predominant and most potent endogenous estrogen. In addition to endogenous estrogens, several man-made and plant-derived molecules, such as bisphenol A and genistein, also exhibit estrogenic activity. Traditionally, the actions of 17β-estradiol are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ, which function as ligand-activated transcription factors. However, 17β-estradiol also mediates rapid signaling events via pathways that involve transmembrane ERs, such as G-protein-coupled ER 1 (GPER; formerly known as GPR30). In the past 10 years, GPER has been implicated in both rapid signaling and transcriptional regulation. With the discovery of GPER-selective ligands that can selectively modulate GPER function in vitro and in preclinical studies and with the use of Gper knockout mice, many more potential roles for GPER are being elucidated. This Review highlights the physiological roles of GPER in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer, for which GPER is emerging as a novel therapeutic target and prognostic indicator.
雌激素在体内发挥着深远的作用，调节着女性和男性的生理和病理过程。在绝经前女性中，许多疾病的患病率较低，这归因于 17β-雌二醇的存在，它是主要的、最有效的内源性雌激素。除了内源性雌激素外，一些人工合成和植物衍生的分子，如双酚 A 和染料木黄酮，也具有雌激素活性。传统上，17β-雌二醇的作用归因于两种核雌激素受体（ERs），即 ERα 和 ERβ，它们作为配体激活的转录因子发挥作用。然而，17β-雌二醇还通过涉及跨膜 ER 的途径介导快速信号事件，例如 G 蛋白偶联 ER1（GPER；以前称为 GPR30）。在过去的 10 年中，GPER 已被牵涉到快速信号和转录调节中。随着 GPER 选择性配体的发现，这些配体可以在体外和临床前研究中选择性地调节 GPER 功能，以及使用 Gper 敲除小鼠，GPER 的许多潜在作用正在被阐明。这篇综述强调了 GPER 在生殖、神经、内分泌、免疫和心血管系统中的生理作用，以及它在包括癌症在内的各种疾病中的病理作用，GPER 作为一种新的治疗靶点和预后指标正在出现。
