Lead Generation & Optimization, Screening Berlin, Bayer Schering Pharma AG, 13342 Berlin, Germany.
Steroids. 2010 Aug-Sep;75(8-9):603-10. doi: 10.1016/j.steroids.2009.12.006. Epub 2009 Dec 23.
The female sex hormone estradiol plays an important role in reproduction, mammary gland development, bone turnover, metabolism, and cardiovascular function. The effects of estradiol are mediated by two classical nuclear receptors, estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). In 2005, G-protein-coupled receptor 30 (GPR30) was claimed to act as a non-classical estrogen receptor that was also activated by the ERalpha and ERbeta antagonists tamoxifen and fulvestrant (ICI 182780). Despite many conflicting results regarding the potential role of GPR30 as an estrogen receptor, the official nomenclature was changed to GPER (G-protein-coupled estrogen receptor). This review revisits the inconsistencies that still exist in the literature and focuses on selected publications that basically address the following two questions: what is the evidence for and against the hypothesis that GPR30 acts as an estrogen receptor? What is the potential in vivo role of GPR30? Thus, in the first part we focus on conflicting results from in vitro studies analysing the subcellular localization of GPR30, its ability to bind (or not to bind) estradiol and to signal (or not to signal) in response to estradiol. In the second part, we discuss the strengths and limitations of four available GPR30 mouse models. We elucidate the potential impact of different targeting strategies on phenotypic diversity.
雌激素是一种女性性激素，在生殖、乳腺发育、骨转换、代谢和心血管功能中起着重要作用。雌激素的作用是通过两种经典的核受体，即雌激素受体 alpha（ERalpha）和雌激素受体 beta（ERbeta）介导的。2005 年，G 蛋白偶联受体 30（GPR30）被认为是一种非经典的雌激素受体，也可以被 ERalpha 和 ERbeta 的拮抗剂他莫昔芬和氟维司群（ICI 182780）激活。尽管关于 GPR30 是否可以作为雌激素受体的潜在作用存在许多相互矛盾的结果，但官方命名法已更改为 GPER（G 蛋白偶联雌激素受体）。这篇综述重新审视了文献中仍然存在的不一致之处，并重点关注了一些基本解决以下两个问题的选定出版物：GPR30 作为雌激素受体的假说有哪些证据支持和反对？GPR30 在体内的潜在作用是什么？因此，在第一部分中，我们重点讨论了分析 GPR30 亚细胞定位、结合（或不结合）雌激素以及对雌激素作出反应（或不作出反应）的能力的体外研究中的相互矛盾的结果。在第二部分中，我们讨论了四种可用的 GPR30 小鼠模型的优缺点。我们阐明了不同靶向策略对表型多样性的潜在影响。
