Membrane Progesterone Receptors (mPRs, PAQRs): Review of Structural and Signaling Characteristics.

Abstract

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.