Antiandrogens: selective androgen receptor modulators.
Antiandrogens can efficiently block androgen receptor (AR) mediated gene expression, and are therefore useful tools in the treatment of androgen dependent prostate cancer. Antiandrogens are either complete or partial inhibitors of AR activity, depending on the nature of the compound. As compared to androgens, antiandrogens induce a different AR conformation, thereby influencing the recruitment of co-regulators (coactivators and corepressors). This ligand-selective modulation of AR activity is affected by an AR mutation (Thr877Ala substitution) found in prostate cancer. In contrast to the wild-type AR, the mutant AR conformation induced by cyproterone acetate (CPA) and hydroxyflutamide (OHF) is comparable to that induced by androgens. As a consequence, this might affect recruitment of co-regulators, thereby allowing CPA and OHF to act as strong agonists on the mutant AR.
Berrevoets
Cor A
CA
Department of Reproduction and Development, Erasmus University Medical Centre Rotterdam, PO Box 1738, DR-3000 Rotterdam, The Netherlands.
Umar
Arzu
A
Brinkmann
Albert O
AO
D000726:Androgen Antagonists / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D015741:Metribolone / Q000378:metabolism; D015735:Mifepristone / Q000378:metabolism; D011485:Protein Binding; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen; D015741:Metribolone; D015735:Mifepristone