Bisphenol AF is a full agonist for the estrogen receptor ERα but a highly specific antagonist for ERβ

Abstract

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 ERα and ERβ and the bisphenol A-specific estrogen-related receptor ERRγ, and to clarify structural characteristics of receptors that influence bisphenol AF binding. Methods: We examined receptor-binding activities of bisphenol AF relative to [3H]17β-estradiol (for ERα and ERβ) and [3H]bisphenol A (for ERRγ). 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 ERRγ. Furthermore, bisphenol AF receptor-binding activity was three times stronger for ERβ [IC50 (median inhibitory concentration) = 18.9 nM] than for ERα. When examined using a reporter gene assay, bisphenol AF was a full agonist for ERα. In contrast, it was almost completely inactive in stimulating the basal constitutive activity of ERβ. Surprisingly, bisphenol AF acted as a distinct and strong antagonist against the activity of the endogenous ERβ agonist 17β-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 ERα and/or ERβ.