Bisphenol AF Is a Full Agonist for the Estrogen Receptor ERα but a Highly Specific Antagonist for ERβ

BACKGROUND: Bisphenol AF has been acknowledged to be useful for the production of CF3-containing polymers with improved chemical, thermal, and mechanical properties. Because of the lack of adequate toxicity data, bisphenol AF has been nominated for comprehensive toxicological characterization. OBJECTIVES: We aimed to determine the relative preference of bisphenol AF for the human nuclear estrogenic receptors ER alpha and ER beta and the bisphenol A-specific estrogen-related receptor ERR gamma, and to clarify structural characteristics of receptors that influence bisphenol AF binding. METHODS: We examined receptor-binding activities of bisphenol AF relative to [H-3] 17 beta-estradiol (for ER alpha and ER beta) and [H-3] bisphenol A (for ERR gamma). Functional luciferase reporter gene assays were performed to assess receptor activation in HeLa cells. RESULTS: We found that bisphenol AF strongly and selectively binds to ERs over ERR gamma. Furthermore, bisphenol AF receptor-binding activity was three times stronger for ER beta [IC50 (median inhibitory concentration) = 18.9 nM] than for ER alpha. When examined using a reporter gene assay, bisphenol AF was a full agonist for ER alpha. In contrast, it was almost completely inactive in stimulating the basal constitutive activity of ER beta. Surprisingly, bisphenol AF acted as a distinct and strong antagonist against the activity of the endogenous ER beta agonist 17 beta-estradiol. CONCLUSION: Our results suggest that bisphenol AF could function as an endocrine-disrupting chemical by acting as an agonist or antagonist to perturb physiological processes mediated through ER alpha and/or ER beta.