Biological function and mode of action of the androgen receptor
E. M. Wilson
Laboratories for Reproductive Biology, and the Department
of Pediatrics and the Department of Biochemistry and Biophysics, University
of North Carolina, Chapel Hill, NC 27599, USA
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.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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