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Progestin and adipoQ receptor family member 7 (PAQR7), also known as membrane progesterone receptor alpha (mPR alpha), is a seven-transmembrane protein that mediates rapid, non-genomic actions of progesterone (UniProt Q86WK9). Unlike classical nuclear progesterone receptors, PAQR7 is localized to the plasma membrane and triggers intracellular signaling pathways such as the inhibition of adenylyl cyclase or activation of MAP kinases (PubMed 12819348). It plays a critical role in reproductive processes, including oocyte maturation and sperm hyperactivation, and has been implicated in neuroprotective mechanisms within the central nervous system (PubMed 23892098). In oncology, PAQR7 expression is often altered in breast, ovarian, and prostate cancers, where it may influence tumor cell migration and apoptosis (PubMed 25533012). While it is a potential therapeutic target for hormonal disorders and certain cancers, its structural distinction from G protein-coupled receptors (GPCRs) despite having seven transmembrane domains remains a subject of scientific discussion. Drugs targeting PAQR7 aim to modulate these rapid progesterone responses without necessarily engaging the slower, genomic pathways of classical receptors.
Modulation of non-genomic progesterone signaling via membrane-bound receptors, typically involving G-protein activation (Gi/o) and subsequent inhibition of adenylyl cyclase or activation of the MAPK/ERK pathway (PubMed 12819348).
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