Fernandes Maria Sofia, Brosens Jan J, Gellersen Birgit
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom.
Steroids. 2008 Oct;73(9-10):942-52. doi: 10.1016/j.steroids.2007.12.004. Epub 2007 Dec 14.
The recent discovery of three closely related cell surface receptors that bind to progesterone and mediate its actions on various cytoplasmic signalling cascades has been heralded as a major break-through. The reason for this is all too obvious. Progesterone is an essential regulator of all major reproductive events and progestins and antiprogestins are widely used in the treatment of many different gynaecological and obstetrical disorders. The novel membrane progestin receptors (mPRalpha, beta, gamma) reportedly resemble and function as G-protein-coupled receptors and therefore are promising pharmaceutical targets. However, our studies failed to corroborate that mPRs are expressed on the cell surface, that they mediate rapid progesterone signalling events, and even that they are bona fide progestin binding moieties. While the reason for these startling opposing results remains unclear, a critical review of existing data may help to shed some light onto the controversial mPRs. Time has come to talk.
最近发现了三种与孕酮结合并介导其对各种细胞质信号级联反应作用的密切相关的细胞表面受体，这一发现被誉为一项重大突破。原因非常明显。孕酮是所有主要生殖事件的重要调节因子，孕激素和抗孕激素广泛用于治疗许多不同的妇科和产科疾病。据报道，新型膜孕激素受体（mPRα、β、γ）类似于G蛋白偶联受体并发挥其功能，因此是有前景的药物靶点。然而，我们的研究未能证实mPRs在细胞表面表达，它们介导快速的孕酮信号事件，甚至未能证实它们是真正的孕激素结合部分。虽然这些惊人的相反结果的原因尚不清楚，但对现有数据进行批判性回顾可能有助于揭示这些有争议的mPRs。是时候展开讨论了。
