Differential Estrogenic Actions of Endocrine-Disrupting Chemicals Bisphenol A, Bisphenol AF, and Zearalenone through Estrogen Receptor α and β in Vitro

• Published in: Environmental health perspectives Vol. 120; no. 7; pp. 1029 - 1035
• Main Authors: Li, Yin, Burns, Katherine A., Arao, Yukitomo, Luh, Colin J., Korach, Kenneth S.
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01-07-2012; US Department of Health and Human Services
• Subjects: Agonists; Benzhydryl Compounds; Biological and medical sciences; Bisphenols; Cell Line; Cell lines; Chemical hazards; Endocrine Disruptors - toxicity; Environment. Living conditions; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Estrogen receptors; Estrogens; HeLa Cells; Hep G2 Cells; Humans; Journalism; Medical sciences; Phenols - toxicity; Plant poisons toxicology; Plasmids; Public health. Hygiene; Public health. Hygiene-occupational medicine; Toxicology; Vehicles; Zearalenone - toxicity; Mimetic hormone; ERβ; ERα; Chemical compound; Mycotoxin; Estrogen; Zearalenone; Endocrine disruptor; BPAF; In vitro; ERα mutants; Toxin; Bisphenol A; Estrogen receptor α; BPA; Health and environment; ERE
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.1104689

Background: Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogen-like activity is attributed to EDCs, such as bisphenol A (BPA), bisphenol AF (BPAF), and zearalenone (Zea), but mechanisms of action and diversity of effects are poorly understood. Objectives: We used in vitro models to evaluate the mechanistic actions of BPA, BPAF, and Zea on estrogen receptor (ER) α and ERβ. Methods: We used three human cell lines (Ishikawa, HeLa, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ERa and ERβ. Ishikawa/ERα stable cells were used to determine changes in estrogen response element (ERE)-mediated target gene expression or rapid action-mediated effects. Results: The three EDCs showed strong estrogenic activity as agonists for ERα in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ERα in Ishikawa cells and BPAF acted as an antagonist for ERβ in HeLa cells, whereas Zea was only a partial antagonist for ERα. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ERα, but Zea activated via both the AF-1 and AF-2 (unctions. Endogenous ERα target genes and rapid signaling via the p44/42 MAPK pathway were activated by BPA, BPAF, and Zea. Conclusion: BPA and BPAF can function as EDCs by acting as cell type-specific agonists (≥ 10 nM) or antagonists (≤ 10 nM) for ERα and ERβ. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 (unctions of ERα. In addition, all three compounds induced the rapid action-mediated response for ERα.