G protein-coupled receptor family C group 6 member A (GPRC6A) (GPRC6A)

The Putative membrane testosterone G protein-coupled receptor, primarily identified as G protein-coupled receptor family C group 6 member A (GPRC6A), is a cell surface receptor that mediates the rapid, non-genomic actions of testosterone (Benten et al., 1999; Pi et al., 2010). Unlike the classical intracellular androgen receptor (AR), which functions as a transcription factor, this GPCR triggers immediate signaling events such as phospholipase C (PLC) activation and the mobilization of intracellular calcium stores (Benten et al., 1999; Benten et al., 2004). It was first characterized in the IC-21 macrophage cell line, which lacks the classical AR but exhibits specific, pertussis toxin-sensitive responses to testosterone (Benten et al., 1999). GPRC6A is a multi-ligand receptor that also senses L-amino acids, cations, and the bone-derived hormone osteocalcin, playing a vital role in coordinating energy metabolism, insulin secretion, and testosterone production (Pi et al., 2010; Ko et al., 2015). It is considered a potential therapeutic target for conditions such as type 2 diabetes, osteoporosis, and prostate cancer, as well as for modulating inflammatory responses in macrophages (Pi et al., 2010; Ko et al., 2015). Its ability to mediate androgen signaling independently of the classical AR offers a pathway for developing selective therapies that minimize the side effects associated with traditional steroid treatments (Pi et al., 2010).

Other names

mAR (Benten et al., 2004)GPCRT (Benten et al., 1999)Membrane androgen receptor (Thomas et al., 2014)Putative membrane testosterone G protein-coupled receptor (Benten et al., 1999)GPRC6A (Pi et al., 2010)

Agonist (Benten et al., 1999; Pi et al., 2010)