BISPHENOL-A INTERACTS WITH THE ESTROGEN-RECEPTOR-ALPHA IN A DISTINCT MANNER FROM ESTRADIOL

We investigated the interaction of bisphenol a (BPA, an estrogenic env ironmental contaminant used in the manufacture of plastics) with the e strogen receptor alpha (ER alpha) transfected into the human HepG2 hep atoma cell line and expanded the study in vivo to examine the effect o f BPA on the immature rat uterus. Bisphenol A was 26-fold less potent in activating ER-WT and was a partial agonist with the ERa compared to E-2. The use of ERa mutants in which the AF1 or AF2 regions were inac tivated has permitted the classification of ER ligands into mechanisti cally distinct groups. The pattern of activity of BPA with the ER alph a mutants differed from the activity observed with weak estrogens (est rone and estriol), partial ER alpha agonists (raloxifene or 4-OH-tamox ifen), or a pure antagonist (ICI 182, 780). Intact immature female Spr ague-Dawley rats were exposed to BPA alone or with E-2 for 3 days. Unl ike E-2, BPA had no effect on uterine weight; however, like E-2, both peroxidase activity and PR levels were elevated, though not to the lev el induced by E-2. Following simultaneous administration, BPA antagoni zed the E-2 stimulatory effects on both peroxidase activity and PR lev els but did not inhibit E-2-induced increases of uterine weight. These results demonstrate that BPA is not merely a weak estrogen mimic but exhibits a distinct mechanism of action at the ER alpha. (C) 1998 Else vier Science Ireland Ltd. All rights reserved.