The androgen receptor (AR, gene AR on Xq12) is a ligand-activated transcription factor of the steroid receptor family. It has the canonical four-domain architecture: an N-terminal transactivation domain containing the polymorphic polyglutamine tract, a zinc-finger DNA-binding domain, a hinge with the nuclear localisation signal, and a C-terminal ligand-binding domain.
How it works, and why it matters
Unliganded AR sits in the cytoplasm bound to heat-shock chaperones. Testosterone or dihydrotestosterone binding triggers chaperone release, an N-terminal/C-terminal interaction, dimerisation and nuclear translocation, after which the dimer occupies androgen response elements and recruits coactivators such as SRC family members. Tissue response depends heavily on local enzymology: 5-alpha-reductase converts testosterone to the higher-affinity DHT in prostate and skin, while aromatase diverts it to estradiol elsewhere.
That enzymology is the whole premise of the SARM field — non-steroidal ligands are not reductase or aromatase substrates, so their tissue profile differs from a steroid. AR is also the readout in prostate cancer research, where antagonists and degraders are the therapeutic class, and receptor mutations in the ligand-binding domain are a documented resistance route.
Related terms and material
gonadotropin · myostatin · in vitro. Reference material: SARMs, MK-2866 (ostarine). Further reading: RAD-140 vs LGD-4033.