Membrane androgen receptor

Membrane androgen receptors (mARs) are a group of G protein-coupled receptors (GPCRs), which bind and are activated by testosterone and/or other androgens.^[1][2][3] Unlike the androgen receptor (AR), a nuclear receptor which mediates its effects via genomic mechanisms, mARs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades.^[2][3] Known or proposed mARs include ZIP9 and GPRC6A.^[2][4]

GPRC6A has been found to be involved in testicular function and prostate cancer.^[2][3] mARs have also been found to be expressed in breast cancer cells.^[5] Activation of mARs by testosterone has been found to increase skeletal muscle strength, indicating potential anabolic effects.^[6] mARs have also been implicated in the antigonadotropic effects of androgens.^[7] 3α-Androstanediol, an active metabolite of dihydrotestosterone (DHT) and a weak androgen as well as a neurosteroid via acting as a positive allosteric modulator of the GABA_A receptor, rapidly influences sexual receptivity and behavior in animals, an effect that is GABA_A receptor-dependent.^[7]

GPR133 binds androgens, specifically the androgen 5α-dihydrotestosterone (5α-DHT).^[8] GPR133 is an adhesion G protein-coupled receptor that functions as a membrane receptor for androgens. When activated by 5α-DHT, GPR133 increases intracellular cyclic AMP (cAMP) levels in muscle cells, leading to enhanced muscle strength.^[8]

See also

• Membrane steroid receptor