Agonists, but not antagonists, alter the conformation of the hormone-binding domain of androgen receptor.

Androgen receptors synthesized by translation in vitro form dimeric aporeceptor complexes with an androgen response element (ARE). Physiological and synthetic androgens elicit a conformational change in the receptor, which increases the mobility of receptor-ARE complexes in gel retardation assays. Neither a steroidal (cyproterone acetate) nor a non-steroidal (casodex) antiandrogen brings about the same effect and, at high concentrations, reverse the action of androgen agonists. When receptor-agonist complexes are subjected to a limited trypsin or chymotrypsin digestion, a protease-resistant 30-kDa fragment corresponding to the entire ligand-binding domain is formed. A similar fragment is not protected in the presence of antiandrogens. The C-terminal origin of the protected region was verified using mutated receptor forms: a mutant with a large N-terminal deletion behaves like the wild-type protein, but the properties of a hormone binding-negative receptor, due to a single-base substitution at codon 807, are not influenced by androgen agonists or antagonists.