THE INHIBITION OF ESTROGEN RECEPTOR-MEDIATED RESPONSES BY CHLORO-S-TRIAZINE-DERIVED COMPOUNDS IS DEPENDENT ON ESTRADIOL CONCENTRATION IN YEAST

The chloro-S-triazine derived compounds atrazine, atrazine desisopropy l, cyanazine, and simazine are commonly used herbicides. These compoun ds do wt have estrogenic activity in yeast expressing human estrogen r eceptor (hER) and an estrogen-sensitive reporter. In the presence of a concentration of estradiol (20 nM) that induced maximal reporter acti vity in yeast, the triazines did not inhibit reporter activity. Howeve r, the triazines decreased reporter activity in a dose-dependent manne r in the presence of a submaximal concentration of estradiol (0.5 nM). The estradiol-dependent activity of a mutant hER lacking the amino te rminus was not inhibited by the triazines in yeast Competition binding assays demonstrated that the triazines displaced radiolabeled estradi ol from recombinant hER. These results suggest that the ability of the triazines to inhibit estrogen receptor-mediated responses in yeast oc cur through their interaction with hER and is dependent on the concent ration of estradiol. (C) 1996 Academic Press, Inc.