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Updated: Jun 13, 2026

Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay
Published on: June 7, 2020
Bisphenol AF is a full agonist for the estrogen receptor ERalpha but a highly specific antagonist for ERbeta
Ayami Matsushima1, Xiaohui Liu, Hiroyuki Okada
1Laboratory of Structure-Function Biochemistry, Department of Chemistry, Research-Education Centre of Risk Science, Faculty and Graduate School of Sciences, Kyushu University, Fukuoka, Japan.
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 ERalpha and ERbeta and the bisphenol A-specific estrogen-related receptor ERRgamma, and to clarify structural characteristics of receptors that influence bisphenol AF binding.
Methods:
We examined receptor-binding activities of bisphenol AF relative to [3H]17beta-estradiol (for ERalpha and ERbeta) and [3H]bisphenol A (for ERRgamma). 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 ERRgamma. Furthermore, bisphenol AF receptor-binding activity was three times stronger for ERbeta [IC50 (median inhibitory concentration) = 18.9 nM] than for ERalpha. When examined using a reporter gene assay, bisphenol AF was a full agonist for ERalpha. In contrast, it was almost completely inactive in stimulating the basal constitutive activity of ERbeta. Surprisingly, bisphenol AF acted as a distinct and strong antagonist against the activity of the endogenous ERbeta agonist 17beta-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 ERalpha and/or ERbeta.
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