Androgen Receptor

The androgen receptor (AR; the AR gene lies on Xq12) is a steroid-receptor-family transcription factor that becomes active when a ligand binds. It follows the classic four-domain layout: an N-terminal transactivation domain that includes the variable polyglutamine repeat, a DNA-binding domain built from zinc fingers, a hinge region holding the nuclear localisation signal, and a ligand-binding domain at the C-terminus.

Mechanism and research relevance

Without a ligand, AR stays in the cytoplasm, held by heat-shock chaperones. Once testosterone or dihydrotestosterone binds, the chaperones are released, the N- and C-terminal regions interact, the receptor dimerises and enters the nucleus; there the dimer binds androgen response elements and recruits coactivators, SRC family proteins among them. How a tissue responds depends strongly on its local enzymes: 5-alpha-reductase turns testosterone into the more potent DHT in prostate and skin, whereas aromatase converts it to estradiol in other tissues.

The SARM concept rests entirely on that enzymology: non-steroidal ligands are substrates for neither reductase nor aromatase, so they act on tissues differently from a steroid. AR is likewise the key readout in prostate cancer research, where antagonists and degraders form the therapeutic class and mutations in the ligand-binding domain are an established resistance mechanism.

Related terms and material

gonadotropin · myostatin · in vitro. Reference material: SARMs, MK-2866 (ostarine). Further reading: RAD-140 vs LGD-4033.