膜孕激素受体(mPRs)的作用,属于孕激素和脂肪Q受体(PAQR)家族,在快速调解中,非基因组(非经典)孕激素作用自20年前鉴定以来已被广泛研究。尽管mPRs与脊椎动物中许多生殖和非生殖功能的孕激素调节有关,直到最近,它们的结构和信号功能的几个关键方面仍未解决,并且仍然是相当大的辩论主题。本文简要回顾了我们对mPRs结构和功能特征的理解的最新进展。提出的mPRα膜拓扑,其配体结合位点的结构,类固醇的结合亲和力是根据其他PAQRs的结构从同源性建模中预测的,脂联素受体,并通过突变分析和配体结合测定证实。综述了大量数据,这些数据表明mPR依赖性孕激素通过mPR调节细胞内信号是由G蛋白的激活介导的。mPRα与孕激素膜受体成分1(PGRMC1)密切相关,已在几种脊椎动物模型中证明了其作为衔接蛋白介导mPRα和mPRα依赖性孕激素信号传导的细胞表面表达的作用。此外,有证据表明,mPRs可以调节其他激素受体的活性。
The role of membrane progesterone receptors (mPRs), which belong to the progestin and adipoQ receptor (PAQR) family, in mediating rapid, nongenomic (non-classical) progestogen actions has been extensively studied since their identification 20 years ago. Although the mPRs have been implicated in progestogen regulation of numerous reproductive and non-reproductive functions in vertebrates, several critical aspects of their structure and signaling functions have been unresolved until recently and remain the subject of considerable debate. This paper briefly reviews recent developments in our understanding of the structure and functional characteristics of mPRs. The proposed membrane topology of mPRα, the structure of its ligand-binding site, and the binding affinities of steroids were predicted from homology modeling based on the structures of other PAQRs, adiponectin receptors, and confirmed by mutational analysis and ligand-binding assays. Extensive data demonstrating that mPR-dependent progestogen regulation of intracellular signaling through mPRs is mediated by activation of G proteins are reviewed. Close association of mPRα with progesterone membrane receptor component 1 (PGRMC1), its role as an adaptor protein to mediate cell-surface expression of mPRα and mPRα-dependent progestogen signaling has been demonstrated in several vertebrate models. In addition, evidence is presented that mPRs can regulate the activity of other hormone receptors.