Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 294, Issue 4, Pages 779-784Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0006-291X(02)00564-8
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The action of nuclear receptor ligands in target tissues is specified mainly by the expression levels of their cognate nuclear receptors. The expression levels of these receptors are controlled through transcriptional and post-transcriptional events. Among post-transcriptional events, the effect of ligand on nuclear receptor protein turnover still remains largely unknown. Therefore, we studied the effects of agonist and antagonists on the turnover of the human androgen receptor (hAR) protein in stably transformed Chinese hamster ovary cells expressing exogenous hAR. Western blot analysis showed that the most potent androgen, dihydrotestosterone (DHT), stabilizes hAR with the induction of the transactivation function of hAR. However, this androgen-induced stabilization of hAR protein was abrogated by well-known androgen antagonists, hydroxyflutamide and bicalutamide (BIC), with inhibition of the transactivation function of hAR. Thus, the present study suggests that androgen antagonists exert their effects through, at least in part, abrogating the agonist-induced stabilization of hAR protein as well as blocking the ligand-induced transactivation function of hAR. (C) 2002 Elsevier Science (USA). All rights reserved.
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