ACTIVATION OF RAT ANDROGEN RECEPTOR BY ANDROGENIC LIGANDS IS UNAFFECTED BY ANTIANDROGENS IN SACCHAROMYCES-CEREVISIAE

The E. coli lacZ has been utilized as a reporter to evaluate ligand-me diated activation of the rat androgen receptor (AR) in Saccharomyces c erevisiae strain YCR1. beta-galactosidase activity was androgen-specif ic and was found to be inducible similar to 260-fold by dihydrotestost erone (DHT), testosterone and R1881. None of the antiandrogens tested was able to antagonize the DHT-dependent induction of beta-galactosida se activity. In the gel retardation assay, exposure of the receptor to DHT in vitro led to the formation of a protein-DNA complex that was n ot detected in yeast extracts unexposed to hormone. However, activatio n of AR by a steroidal (cyproterone acetate) and a non-steroidal antia ndrogen (flutamide) either alone or in combination with DHT also resul ts in a similar migration pattern. Additionally, LEM1, the ABC transpo rter that selectively modulates the biological potency of steroids in yeast, although operative in YCR1, was not responsible for antiandroge n resistance. These results thus indicate the involvement of other non -receptor factor(s) in mediating the effect of antiandrogens in yeast. (C) 1998 Elsevier Science B.V.