ToxSci Advance Access published online on April 20, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj204
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1 Department of Biology, Faculty of Science, Shizuoka University, Shizuoka, Japan
* To whom correspondence should be addressed. We investigated the effects of the brominated phenolic and phenol compounds, some of which are brominated flame retardants, on the binding of [125I]3,3',5-L-triiodothyronine ([125I]T3) to purified Xenopus laevis transthyretin (xTTR) and to the ligand-binding domain of X. laevis thyroid hormone receptor
Received February 17, 2006
Accepted April 16, 2006
Endocrine Toxicology
In Vitro and In Vivo Analysis of the Thyroid System-Disrupting Activities of Brominated Phenolic and Phenol Compounds in Xenopus laevis
Yumiko Kudo 1,
Kiyoshi Yamauchi 1 *,
Hitoshi Fukazawa 2,
and
Yoshiyasu Terao 3
2 Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan
3 Institute for Environmental Sciences, University of Shizuoka, Shizuoka, Japan
Kiyoshi Yamauchi, E-mail: sbkyama{at}ipc.shizuoka.ac.jp
Abstract 
(xTR LBD), on the induction of a T3-responsive reporter gene in a recombinant X. laevis cell line (XL58-TRE-Luc) and on T3-induced or spontaneous metamorphosis in X. laevis tadpoles. Of the brominated phenolic and phenol compounds tested, 3,3',5-tribromobisphenol A and 3,3'-dibromobisphenol A were the most potent competitors of [125I]T3 binding to xTTR and the xTR LBD, respectively. Structures with a bromine in either ortho positions with respect to the hydroxy group, competed more efficiently with T3 binding to xTTR and the xTR LBD. 3,3',5-Tribromobisphenol A and 3,3',5,5'-tetrabromobisphenol A, at 0.1-1.0 µM, exerted both T3-agonist and -antagonist activities in the T3-responsive reporter gene assay. Sera obtained from fetal bovine and bullfrog tadpoles weakened the T3-agonist and -antagonist activities of 3,3',5-tribromobisphenol A, but not the T3-antagonist activity of o-t-butylphenol, for which xTTR has no significant affinity. The T3-agonist and -antagonist activities of 0.5 µM 3,3',5-tribromobisphenol A were confirmed in the in vivo short-term gene expression assay in premetamorphic X. laevis tadpoles using endogenous T3-responsive genes as molecular markers. Our results suggest that 3,3',5-tribromobisphenol A affects T3 binding to xTTR and xTR, and that it interferes with the intracellular T3 signalling pathway.
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