Bisphenol A interacts with the estrogen receptor α in a distinct manner from estradiol
Abstract
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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In hippocampal glutamatergic neurons, BPA binds membrane-associated ERα and, even at low concentrations (10-100 nM), rapidly increases intracellular Ca2+ and activates ERK/MAP kinase signaling.
“In hippocampal glutamatergic neurons, BPA binds membrane-associated ERα and, even at low concentrations (10–100 nM), rapidly increases intracellular Ca2+ and activates ERK/MAP kinase signaling (Gould et al., 1998; Ogiue-Ikeda et al., 2008).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Gould et al., 1998
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“In hippocampal glutamatergic neurons, BPA binds membrane-associated ER α and, even at low concentrations (10–100 nM), rapidly increases intracellular Ca 2+ and activates ERK/ MAP kinase signaling (Gould et al., 1998; Ogiue-Ikeda et al., 2008).”
- Authors
- Gould, J. C., Leonard, L. S., Maness, S. C., Wagner, B. L., Conner, K., Zacharewski, T., Safe, S., McDonnell, D. P., & Gaido, K. W.
- Affiliations
- Duke Medical Center (US)
- Texas A&M University (US)
- Western University (CA)
- Corresponding author
- Gaido, Kevin W.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 142
- Issue
- 1-2
- Pages
- 203-214
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2040879761
- Cited by
- 510
- References
- 0
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 13 · 2023: 13 · 2022: 20 · 2021: 23 · 2020: 22 · 2019: 23 · 2018: 28 · 2017: 29 · 2016: 17 · 2015: 31 · 2014: 33 · 2013: 23 · 2012: 24
- FWCI
- 16.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48807)
- National Institute of Environmental Health Sciences (ES 04917, P42ES004917)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Keywords
- bisphenol A, estrogen receptor alpha, estradiol, partial agonists, immature uterus, uterine weight, progesterone receptor, peroxidase activity
- MeSH terms
- Bisphenol A Compounds, Animals, Benzhydryl Compounds, Estradiol, Estrogens, Non-Steroidal, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Peroxidase, Organ Size, Phenols, Receptors, Estrogen, Receptors, Progesterone, Transfection, Tumor Cells, Cultured, Uterus, Mutagenesis, Rats, Sprague-Dawley, Estrogen Receptor alpha, Rats
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