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

Publication ,  Journal Article
Gould, JC; Leonard, LS; Maness, SC; Wagner, BL; Conner, K; Zacharewski, T; Safe, S; McDonnell, DP; Gaido, KW
Published in: Mol Cell Endocrinol
July 25, 1998

We investigated the interaction of bisphenol A (BPA, an estrogenic environmental contaminant used in the manufacture of plastics) with the estrogen receptor alpha (ERalpha) 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 ERalpha compared to E2. The use of ERalpha 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 ERalpha mutants differed from the activity observed with weak estrogens (estrone and estriol), partial ERalpha 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 ERalpha.

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Published In

Mol Cell Endocrinol

DOI

ISSN

0303-7207

Publication Date

July 25, 1998

Volume

142

Issue

1-2

Start / End Page

203 / 214

Location

Ireland

Related Subject Headings

  • Uterus
  • Tumor Cells, Cultured
  • Transfection
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Rats, Sprague-Dawley
  • Rats
  • Phenols
  • Peroxidase
  • Organ Size
 

Citation

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Gould, J. C., Leonard, L. S., Maness, S. C., Wagner, B. L., Conner, K., Zacharewski, T., … Gaido, K. W. (1998). Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from estradiol. Mol Cell Endocrinol, 142(1–2), 203–214. https://doi.org/10.1016/s0303-7207(98)00084-7
Gould, J. C., L. S. Leonard, S. C. Maness, B. L. Wagner, K. Conner, T. Zacharewski, S. Safe, D. P. McDonnell, and K. W. Gaido. “Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from estradiol.Mol Cell Endocrinol 142, no. 1–2 (July 25, 1998): 203–14. https://doi.org/10.1016/s0303-7207(98)00084-7.
Gould JC, Leonard LS, Maness SC, Wagner BL, Conner K, Zacharewski T, et al. Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from estradiol. Mol Cell Endocrinol. 1998 Jul 25;142(1–2):203–14.
Gould, J. C., et al. “Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from estradiol.Mol Cell Endocrinol, vol. 142, no. 1–2, July 1998, pp. 203–14. Pubmed, doi:10.1016/s0303-7207(98)00084-7.
Gould JC, Leonard LS, Maness SC, Wagner BL, Conner K, Zacharewski T, Safe S, McDonnell DP, Gaido KW. Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from estradiol. Mol Cell Endocrinol. 1998 Jul 25;142(1–2):203–214.
Journal cover image

Published In

Mol Cell Endocrinol

DOI

ISSN

0303-7207

Publication Date

July 25, 1998

Volume

142

Issue

1-2

Start / End Page

203 / 214

Location

Ireland

Related Subject Headings

  • Uterus
  • Tumor Cells, Cultured
  • Transfection
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Rats, Sprague-Dawley
  • Rats
  • Phenols
  • Peroxidase
  • Organ Size