Differential estrogenic actions of endocrine-disrupting chemicals bisphenol A, bisphenol AF, and zearalenone through estrogen receptor ? and ? in vitro.

ABSTRACT:

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) ? and ER?.

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 ER? and ER?. Ishikawa/ER? 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? in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ER? in Ishikawa cells and BPAF acted as an antagonist for ER? in HeLa cells, whereas Zea was only a partial antagonist for ER?. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ER?, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ER? 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? and ER?. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ER?. In addition, all three compounds induced the rapid action-mediated response for ER?.

SUBMITTER: Li Y 

PROVIDER: S-EPMC3404668 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature