Biological function and mode of action of the androgen receptor

Abstract

Chemical contaminants with antiandrogen or androgen activity have been identified in the environment. The mode of action of these endocrine disruptors derives from their ability to bind to the androgen receptor (AR), a member of the steroid receptor family of nuclear receptors. The AR is a ligand-activated transcription factor with properties unique among members of the steroid receptor family. Binding of endocrine disruptors to the AR impacts its ability to activate or inhibit AR-regulated genes. Most notable of these are the agonist-induced and antagonist-inhibited interdomain interactions that influence AR stability and function. Environmental antiandrogens identified thus far are metabolites of pesticides and herbicides, exerting androgen antagonist effects by blocking AR-induced gene transcription required for male sexual development. Environmental androgens can be precursors of the naturally occurring biologically active androgens testosterone and dihydrotestosterone or result from anabolic steroid use in the livestock industry. They have agonist activity by their ability to bind the AR and mimic the natural hormone, increasing AR-mediated transcription of androgen-responsive genes. The presence of masculinized female fish in polluted rivers indicates the presence of androgen-like pollutants in the environment.