INHIBITION OF PROGESTERONE-RECEPTOR ACTIVITY IN YEAST BY SYNTHETIC CHEMICALS

Numerous synthetic chemicals have estrogenic activity by interacting w ith the estrogen receptor. In this report, we test the hypothesis that some estrogenic chemicals may also modulate the human progesterone re ceptor (hPR) signaling pathway. This was evaluated by examining synthe tic chemicals for their ability to modulate the activity of hPR expres sed in yeast. The transcriptional activity of hPR was not increased in the presence of several synthetic chemicals. However, the estrogenic chemicals p-nonylphenol and 4-tert-octylphenol, and pentachlorophenol, effectively inhibited the activity of the hPR in yeast. Competition b inding studies indicated these chemicals effectively competed with rad iolabeled R5020, a synthetic progestin, for binding to the hPR in yeas t. These results indicate that some synthetic chemicals directly inhib it the activity of hPR in yeast. The observations that some estrogenic chemicals can also inhibit hPR activity suggest a potential mechanism for the reported potent estrogenic activities of these chemicals. (C) 1996 Academic Press, Inc.