Rapid effects of steroid hormones were discovered in the early 1950s, but the subject was dominated in the 1970s by discoveries of estradiol and progesterone stimulating protein synthesis. This led to the paradigm that steroid hormones regulate growth, differentiation, and metabolism via binding a receptor in the nucleus. It took 30 years to appreciate not only that some cellular functions arise solely from membrane-localized steroid receptor (SR) actions, but that rapid sex steroid signaling from membrane-localized SRs is a prerequisite for the phosphorylation, nuclear import, and potentiation of the transcriptional activity of nuclear SR counterparts. Here, we provide a review and update on the current state of knowledge of membrane-initiated estrogen (ER), androgen (AR) and progesterone (PR) receptor signaling, the mechanisms of membrane-associated SR potentiation of their nuclear SR homologues, and the importance of this membrane-nuclear SR collaboration in physiology and disease. We also highlight potential clinical implications of pathway-selective modulation of membrane-associated SR.

中文翻译：

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膜启动的雌激素、雄激素和孕激素受体信号在健康和疾病中的作用。

类固醇激素的快速作用是在 20 世纪 50 年代初期发现的，但在 1970 年代，由于雌二醇和黄体酮刺激蛋白质合成的发现而主导了这一主题。这导致类固醇激素通过结合细胞核中的受体来调节生长、分化和新陈代谢的范例。花了 30 年的时间才认识到，不仅一些细胞功能完全来自膜定位类固醇受体 (SR) 的作用，而且来自膜定位 SR 的快速性类固醇信号传导是磷酸化、核输入和增强的先决条件。核SR对应物的转录活性。在这里，我们回顾并更新了膜启动雌激素 (ER)、雄激素 (AR) 和孕激素 (PR) 受体信号转导的当前知识状态，其核 SR 同源物的膜相关 SR 增强机制，以及这种膜-核 SR 协作在生理学和疾病中的重要性。我们还强调了膜相关 SR 的途径选择性调节的潜在临床意义。