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

Janet C. Gould, Linda S. Leonard, Susan C. Maness, Brandee L. Wagner, Kevin Conner, Tim Zacharewski, Steve Safe, Donald P. McDonnell, Kevin W. Gaido

Research output: Contribution to journalArticlepeer-review

433 Scopus citations


We investigated the interaction of bisphenol A (BPA, an estrogenic environmental contaminant used in the manufacture of plastics) with the estrogen receptor alpha (ERα) 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 ERα compared to E2. The use of ERα 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 ERα mutants differed from the activity observed with weak estrogens (estrone and estriol), partial ERα 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 E2 for 3 days. Unlike E2, BPA had no effect on uterine weight; however, like E2, both peroxidase activity and PR levels were elevated, though not to the level induced by E2. Following simultaneous administration, BPA antagonized the E2 stimulatory effects on both peroxidase activity and PR levels but did not inhibit E2-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 ERα.

Original languageEnglish (US)
Pages (from-to)203-214
Number of pages12
JournalMolecular and cellular endocrinology
Issue number1-2
StatePublished - Jul 25 1998


  • Anti-estrogen
  • Bisphenol A
  • Estrogen
  • HepG2 cells
  • Receptor
  • Uterotrophic assay

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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