PMID- 22494775 OWN - NLM STAT- MEDLINE DCOM- 20121031 LR - 20211021 IS - 1552-9924 (Electronic) IS - 0091-6765 (Print) IS - 0091-6765 (Linking) VI - 120 IP - 7 DP - 2012 Jul TI - Differential estrogenic actions of endocrine-disrupting chemicals bisphenol A, bisphenol AF, and zearalenone through estrogen receptor alpha and beta in vitro. PG - 1029-35 LID - 10.1289/ehp.1104689 [doi] AB - 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) alpha and ERbeta. 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 ERalpha and ERbeta. Ishikawa/ERalpha 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 ERalpha in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ERalpha in Ishikawa cells and BPAF acted as an antagonist for ERbeta in HeLa cells, whereas Zea was only a partial antagonist for ERalpha. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ERalpha, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ERalpha 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 (