Pure antiandrogens disrupt the recruitment of coactivator GRIP1 to colocalize with androgen receptor in nuclei.
We have used confocal microscopy to elucidate the effects of antiandrogens on nuclear localization of the androgen receptor (AR) with its transcriptional coactivator GRIP1. We show that the agonist-activated AR recruits GRIP1 to colocalize with the receptor in the nucleoplasm. By contrast, AR complexed to the antiandrogens hydroxyflutamide and bicalutamide fails to influence nuclear distribution of GRIP1. Likewise, the non-steroidal antiandrogens prevent the agonist-induced AR-GRIP1 colocalization from occurring. Androgen antagonists affect nuclear redistribution of AR-GRIP1 in a fashion that parallels their effects on the transcriptional activity of AR, in that the pure antagonists block GRIP1-dependent activation of AR function, whereas the mixed antagonist/agonist cyproterone acetate promotes both AR-driven redistribution of GRIP1 and activation of AR by GRIP1.
Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014, Helsinki, Finland.
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Karvonen
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Jänne
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Palvimo
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D019556:COS Cells / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D002522:Chlorocebus aethiops; D017373:Cyproterone Acetate / Q000494:pharmacology; D005485:Flutamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009570:Nitriles; D051958:Nuclear Receptor Coactivator 2; D011944:Receptors, Androgen / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014105:Tosyl Compounds; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D009570:Nitriles; D051958:Nuclear Receptor Coactivator 2; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D014157:Transcription Factors; C014290:hydroxyflutamide; D017373:Cyproterone Acetate; D005485:Flutamide; C053541:bicalutamide