Bisphenol A interacts with the estrogen receptor α in a distinct manner from estradiol

We investigated the interaction of bisphenol a (BPA, an estrogenic environmental contaminant used in the manufacture of plastics) with the estrogen receptor alpha (ER alpha) transfected into the human HepG2 hepatoma cell line and expanded the study in vivo to examine the effect of 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 inactivated has permitted the classification of ER ligands into mechanistically distinct groups. The pattern of activity of BPA with the ER alpha mutants differed from the activity observed with weak estrogens (estrone and estriol), partial ER alpha agonists (raloxifene or 4-OH-tamoxifen), or a pure antagonist (ICI 182, 780). Intact immature female Sprague-Dawley rats were exposed to BPA alone or with E-2 for 3 days. Unlike 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 level induced by E-2. Following simultaneous administration, BPA antagonized the E-2 stimulatory effects on both peroxidase activity and PR levels 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 Elsevier Science Ireland Ltd. All rights reserved.