The mechanism of action of endocrine-disrupting chemicals Bisphenol A, Bisphenol AF and Zearalenone on estrogen receptors in vitro

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NIEHS	MOLBIO-6

Authors

• Y Li
• K Burns
• Y Arao
• K Korach

Abstract

Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogenic-like activity is attributed to a number of EDCs; however, their mechanisms of action are poorly understood. Three such EDCs are 1. Bisphenol A (BPA), used in the production of plastics, 2. Bisphenol AF (BPAF), a fluorinated derivative of BPA, 3. Zearalenone (Zea), a non-steroidal estrogenic mycotoxin produced by species of fusarium. To evaluate the mechanistic actions of BPA, BPAF and Zea on ERalpha and ERbeta, three human cell lines were used to examine the ERE-mediated promoter activation, and ERalpha stable cells were used to determine changes in ERE-mediated target gene expression or rapid action. These results suggest that BPA and BPAF can act both as agonists at higher concentrations (>10 nM) and as antagonists at lower concentrations (<10 nM) for ERalpha and ERbeta. These actions were cell type specific. BPA and BPAF are able to activate the AF-2 function of ERalpha. Zea has strong estrogenic effects and it may be due to its ability to activate both AF1 and AF2 functions. Additionally, rapid action-mediated response was induced by these three EDCs, suggesting that besides their genomic action they can also mediate rapid action responses involved in endogenous ER signaling actions.

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