Rapid, progestin actions initiated at the cell surface that are often nongenomic have been described in a variety of reproductive tissues, but until recently the identities of the membrane receptors mediating these nonclassical progestins actions remained unclear. Evidence has been obtained in the last 4-5 years for the involvement of two types of novel membrane proteins unrelated to nuclear steroid receptors, progesterone membrane receptors (mPRs) and progesterone receptor membrane component 1 (PGMRC1), in progestin signaling in several vertebrate reproductive tissues and in the brain. The mPRs, (M(W) approximately 40 kDa) initially discovered in fish ovaries, comprise at least three subtypes, alpha, beta and gamma and belong to the seven-transmembrane progesterone adiponectin Q receptor (PAQR) family. Both recombinant and wildtype mPRs display high affinity (K(d) approximately 5 nM), limited capacity, displaceable and specific progesterone binding. The mPRs are directly coupled to G proteins and typically activate pertussis-sensitive inhibitory G proteins (G(i)), to down-regulate adenylyl cyclase activity. Recent studies suggest the alpha subtype (mPRalpha) has important physiological functions in variety of reproductive tissues. The mPRalpha is an intermediary in progestin induction of oocyte maturation and stimulation of sperm hypermotility in fish. In mammals, the mPRalphas have been implicated in progesterone regulation of uterine function in humans and GnRH secretion in rodents. The single-transmembrane protein PGMRC1 (M(W) 26-28 kDa) was first purified from porcine livers and its cDNA was subsequently cloned from porcine smooth muscle cells and a variety of other tissues by different investigators. PGMRC1 and the closely-related PGMRC2 belong to the membrane-associated progesterone receptor (MAPR) family. The PGMRC1 protein displays moderately high binding affinity for progesterone which is 2- to 10-fold greater than that for testosterone and glucocorticoids, and also can bind to other molecules such as heme, cholesterol metabolites and proteins. The signal transduction pathways induced by binding of progesterone to PGMRC1 have not been described to date, although motifs for tyrosine kinase, kinase binding, SH2 and SH3 have been predicted from the amino acid sequence. Evidence has been obtained that PGMRC1 mediates the antiapoptotic affects of progesterone in rat granulosa cells. The PGMRC1 protein may also be an intermediary in the progesterone induction of the acrosome reaction in mammalian sperm. Despite these recent advances, many aspects of progestin signaling through these two families of novel membrane proteins remain unresolved. Biochemical characterization of the receptors has been hampered by rapid degradation of the partially purified proteins. A major technical challenge has been to express sufficient amounts of the recombinant receptors on the plasma membranes in eukaryotic systems to permit investigations of their progestin binding and signal transduction characteristics. Additional basic information on the molecular and cellular mechanisms by which mPRs and PGMRC1 interact with progestins, signal transductions pathways and other proteins will be required to establish a comprehensive model of nontraditional progestin actions mediated through these novel proteins.

中文翻译：

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膜孕激素受体α (mPRα) 和孕激素膜受体成分 1 (PGMRC1) 的特征及其在介导快速孕激素作用中的作用

在细胞表面启动的快速、通常是非基因组的孕激素作用已在各种生殖组织中得到描述，但直到最近，介导这些非经典孕激素作用的膜受体的身份仍不清楚。在过去的 4-5 年中，已经获得了两种与核类固醇受体无关的新型膜蛋白、孕酮膜受体 (mPR) 和孕酮受体膜成分 1 (PGMRC1) 参与几种脊椎动物生殖系统中孕激素信号传导的证据。组织和大脑中。最初在鱼类卵巢中发现的 mPR（M(W) 大约 40 kDa）包括至少三种亚型，α、β 和 γ，属于七跨膜孕酮脂联素 Q 受体 (PAQR) 家族。重组和野生型 mPR 都显示出高亲和力（K(d) 大约 5 nM）、容量有限、可置换和特定的孕酮结合。mPR 直接与 G 蛋白偶联，通常会激活百日咳敏感的抑制性 G 蛋白 (G(i))，以下调腺苷酸环化酶活性。最近的研究表明 α 亚型 (mPRalpha) 在各种生殖组织中具有重要的生理功能。mPRalpha 是孕激素诱导卵母细胞成熟和刺激鱼中精子过度运动的中介物。在哺乳动物中，mPRalphas 与孕酮调节人类子宫功能和啮齿动物 GnRH 分泌有关。单跨膜蛋白 PGMRC1 (M(W) 26-28 kDa) 首先从猪肝脏中纯化，其 cDNA 随后由不同的研究人员从猪平滑肌细胞和各种其他组织中克隆。PGMRC1 和密切相关的 PGMRC2 属于膜相关孕酮受体 (MAPR) 家族。PGMRC1 蛋白对孕酮表现出中等高的结合亲和力，是睾酮和糖皮质激素的 2 到 10 倍，并且还可以与其他分子如血红素、胆固醇代谢物和蛋白质结合。尽管已经从氨基酸序列预测了酪氨酸激酶、激酶结合、SH2 和 SH3 的基序，但迄今为止尚未描述由孕酮与 PGMRC1 结合诱导的信号转导途径。已有证据表明 PGMRC1 介导了孕酮在大鼠颗粒细胞中的抗凋亡作用。PGMRC1 蛋白也可能是孕酮诱导哺乳动物精子顶体反应的中介。尽管最近取得了这些进展，但孕激素信号通过这两个新型膜蛋白家族的许多方面仍未得到解决。部分纯化蛋白质的快速降解阻碍了受体的生化表征。一个主要的技术挑战是在真核系统的质膜上表达足够量的重组受体，以研究它们的孕激素结合和信号转导特性。有关 mPR 和 PGMRC1 与孕激素相互作用的分子和细胞机制的其他基本信息，