Micevych P, Kuo J, Christensen A
Department of Neurobiology, Laboratory of Neuroendocrinology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
J Neuroendocrinol. 2009 Mar;21(4):249-56. doi: 10.1111/j.1365-2826.2009.01833.x.
The best characterised oestrogen receptors (ERs) that are responsible for membrane-initiated oestradiol signalling are the classic ERs, ERalpha and ERbeta. When in the nucleus, these proteins are oestradiol activated transcription factors but, when trafficked to the cell membrane, ERalpha and ERbeta rapidly activate protein kinase pathways, alter membrane electrical properties, modulate ion flux and can mediate long-term effects through gene expression. To initiate cell signalling, membrane ERs transactivate metabotropic glutamate receptors (mGluRs) to stimulate Gq signalling through pathways using PKC and calcium. In this review, we discuss the interaction of membrane ERalpha with metabotropic glutamate receptor 1a (mGluR1a) to initiate rapid oestradiol cell signalling and its critical roles in female reproduction: sexual behaviour and oestrogen positive feedback of the luteinising hormone (LH) surge. Although long considered to be regulated by the long-term actions of oestradiol on gene transcription, recent results indicate that membrane oestradiol cell signalling is vital for a full display of sexual receptivity. Similarly, the source of pre-ovulatory progesterone necessary for initiating the LH surge is hypothalamic astrocytes. Oestradiol rapidly amplifies progesterone synthesis through the release of intracellular calcium stores. The ERalpha-mGluR1a interaction is necessary for critical calcium flux. These two examples provide support for the hypothesis that membrane ERs are not themselves G-protein receptors; rather, they use mGluRs to signal.
负责膜启动的雌二醇信号传导的最具特征的雌激素受体（ERs）是经典的ERs，即ERα和ERβ。当在细胞核中时，这些蛋白质是雌二醇激活的转录因子，但当转运到细胞膜时，ERα和ERβ会迅速激活蛋白激酶途径，改变膜的电特性，调节离子通量，并可通过基因表达介导长期效应。为了启动细胞信号传导，膜ERs通过使用蛋白激酶C（PKC）和钙的途径反式激活代谢型谷氨酸受体（mGluRs）以刺激Gq信号传导。在本综述中，我们讨论膜ERα与代谢型谷氨酸受体1a（mGluR1a）的相互作用，以启动快速的雌二醇细胞信号传导及其在雌性生殖中的关键作用：性行为和促黄体生成素（LH）峰的雌激素正反馈。尽管长期以来人们认为其受雌二醇对基因转录的长期作用调节，但最近的结果表明，膜雌二醇细胞信号传导对于充分表现出性接受能力至关重要。同样，启动LH峰所需的排卵前孕酮的来源是下丘脑星形胶质细胞。雌二醇通过释放细胞内钙储存迅速放大孕酮合成。ERα-mGluR1a相互作用对于关键的钙通量是必需的。这两个例子支持了膜ERs本身不是G蛋白受体的假设；相反，它们利用mGluRs来传递信号。
