Membrane Androgen Receptor(S) and their Role in Prostate Cancer:A Review

Androgen, a steroid hormone, typically mediates its action by binding to the cytosolic Androgen Receptor (AR), via the classical or genomic pathway. Androgens can also act through a non-classical or non-genomic pathway interacting with receptors present on the plasma membrane of cells. Although the identity of the nuclear AR is well established, the identity of the membrane AR is still not clear. Through independent studies, three proteins have been identified that are present on plasma membranes of prostate cells and can mediate androgen signalling, viz, GPRC6A, AR8 and ZIP9. Although these proteins can mediate androgen signalling, the membrane receptor which is used most frequently and specifically for mediating androgen action in prostate cells is not confirmed. Recent research has shown that the non-genomic androgen signalling plays a key role in progression of prostate cancer (PCa). In this review, the potential of these three proteins for their ability to act as the membrane AR has been analysed. The use of membrane AR as a novel target for the treatment of PCa has also been discussed.