Membrane progesterone receptor alpha (mPRα) (mPRα)

Membrane progesterone receptor alpha (mPRα), encoded by the PAQR7 gene, is a seven-transmembrane protein that mediates the rapid, non-genomic effects of progesterone (UniProt Q86WK9). Unlike classical nuclear progesterone receptors (nPRs) which act as transcription factors, mPRα is localized to the plasma membrane and initiates signaling through G proteins, specifically inhibiting adenylyl cyclase and activating the MAPK/ERK and PI3K/Akt pathways (PubMed: 12748342, 15155224). This receptor plays a vital role in reproductive physiology, including the regulation of oocyte maturation, sperm hyperactivation, and GnRH secretion (PubMed: 24631195). In the central nervous system, mPRα is involved in neuroprotective mechanisms and the modulation of neurosteroid-induced behaviors (PubMed: 18448044). Clinically, mPRα is often overexpressed in various malignancies such as breast, ovarian, and endometrial cancers, where it can promote cell survival and migration, making it a significant target for oncological research (PubMed: 28619367). While progesterone is its primary endogenous ligand, synthetic progestins and certain nPR antagonists like mifepristone also interact with the receptor, though with varying affinities (PubMed: 15155224). Developing selective mPRα modulators remains a key therapeutic goal to harness its neuroprotective and anti-cancer potential while minimizing systemic hormonal side effects.

Other names

Progestin and adipoQ receptor family member 7PAQR7mPR alphaMembrane-associated progesterone receptor alphaMembrane progesterone receptor alpha

Agonist binding to mPRα triggers G protein-mediated signaling, leading to the inhibition of adenylyl cyclase and the activation of intracellular kinase cascades such as MAPK/ERK and PI3K/Akt (PubMed: 12748342).