G protein-coupled receptor 101 (GPR101)

G protein-coupled receptor 101 (GPR101) is an orphan class A G protein-coupled receptor expressed predominantly in the brain and pituitary gland, where it is implicated in growth hormone regulation and pituitary development. Its overexpression or gene duplication drives constitutive receptor activity, leading to hypersecretion of growth hormone and prolactin, which underlies the pathogenesis of X-linked acrogigantism and certain cases of acromegaly and pituitary adenoma. GPR101 demonstrates constitutive and ligand-dependent activation of multiple G protein pathways (primarily Gs, but also Gq and G12/13), mediating diverse cellular processes, including signal transduction, immune regulation, and growth signaling. It is emerging as a potential therapeutic target, though no approved drugs currently modulate its function clinically. The recent identification of synthetic and endogenous agonists (e.g., AA-14, RvD5n-3 DPA) and its roles in endocrine and inflammatory signaling emphasize its multifaceted biological significance and therapeutic promise.

Other names

GPCR6PAGH2PITA2probable G-protein coupled receptor 101

Agonists such as AA-14 activate GPR101 by binding to a putative side pocket, inducing G protein signaling (Gs, Gq, and G12/13 pathways) leading to increased cAMP and hormone secretion. Endogenous mediators regulate immune cell function and inflammatory resolution. GnRH-(1-5) transactivates EGFR via GPR101.