Bisphenol AF is a full agonist for the estrogen receptor ERalpha but a highly specific antagonist for ERbeta.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Matsushima
Ayami
A
Laboratory of Structure-Function Biochemistry, Department of Chemistry, Research-Education Centre of Risk Science, Faculty and Graduate School of Sciences, Kyushu University, Fukuoka, Japan.
Liu
Xiaohui
X
Okada
Hiroyuki
H
Shimohigashi
Miki
M
Shimohigashi
Yasuyuki
Y
D001559:Benzhydryl Compounds; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010636:Phenols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds