Progestin and adipoQ receptor 8 (PAQR8)

Progestin and adipoQ receptor 8 (PAQR8), also known as membrane progestin receptor beta (mPR-beta), is a seven-transmembrane protein that mediates rapid, non-genomic actions of progesterone [UniProtKB - Q8TEZ7]. Unlike classical nuclear progesterone receptors that act as transcription factors, PAQR8 resides on the plasma membrane and triggers intracellular signaling cascades [PMID: 12748293]. These cascades include the inhibition of cAMP production through Gi protein coupling and the activation of mitogen-activated protein kinases (MAPK) [PMID: 12748293]. PAQR8 is widely expressed in the central nervous system, where it contributes to neuroprotective effects and the regulation of cilia [NCBI Gene ID: 85378]. In reproductive tissues, it plays a role in oocyte maturation and sperm motility [PMID: 12748293]. In clinical contexts, PAQR8 is frequently dysregulated in various malignancies, such as breast, ovarian, and endometrial cancers, making it a potential target for endocrine-related therapies [PMID: 24631561]. Research into PAQR8-specific ligands aims to harness its signaling pathways for treating neurological and reproductive disorders while minimizing the side effects associated with broad-spectrum progestins. The receptor's distinct signaling profile compared to nuclear receptors offers a unique avenue for drug development in hormone-sensitive conditions.

Other names

Membrane progestin receptor betamPR-betamPR betaMPRB

Agonist at the membrane progestin receptor beta, leading to Gi-mediated inhibition of adenylyl cyclase and activation of MAPK/ERK signaling pathways [PMID: 12748293].