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

作者：Li Yin; Burns Katherine A; Arao Yukitomo; Luh Colin J; Korach Kenneth S^*

来源：Environmental Health Perspectives, 2012, 120(7): 1029-1035.

DOI：10.1289/ehp.1104689

• BPA
• BPAF
• ER alpha
• ER alpha mutants
• ER beta
• ERE
• estrogen
• zearalenone

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 ER beta.
METHODS: We used three human cell lines (Ishikawa, He La, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ER alpha and ER beta. Ishikawa/ER alpha 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 ER alpha in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ER alpha in Ishikawa cells and BPAF acted as an antagonist for ER beta in He La cells, whereas Zea was only a partial antagonist for ER alpha. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ER alpha, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ER alpha 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 ER alpha and ER beta. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ER alpha. In addition, all three compounds induced the rapid action-mediated response for ER alpha.

• 出版日期2012-7