title: Anti-thyroid hormonal activity of tetrabromobisphenol A, a flame retardant, and related compounds: Affinity to the mammalian thyroid hormone receptor, and effect on tadpole metamorphosis.
abstract: The thyroid hormone-disrupting activity of tetrabromobisphenol A (TBBPA), a flame retardant, and related compounds was examined. TBBPA, tetrachlorobisphenol A (TCBPA), tetramethylbisphenol A (TMBPA) and 3,3'-dimethylbisphenol A (DMBPA) markedly inhibited the binding of triiodothyronine (T3; 1 x 10(-10) M) to thyroid hormone receptor in the concentration range of 1 x 10(-7)-1 x 10(-4) M, while bisphenol A and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA and DMBPA did not exhibit thyroid hormonal activity in a thyroid hormone-responsive reporter assay using a Chinese hamster ovary cell line (CHO-K1) transfected with thyroid hormone receptor alpha1 or beta1, but TBBPA and TCBPA showed significant anti-thyroid hormone effects on the activity of T3 (1 x 10(-8) M) in the concentration range of 3 x 10(-6) - 5 x 10(-5) M. The thyroid hormone-disrupting activity of TBBPA was also examined in terms of the effect on amphibian metamorphosis stimulated by thyroid hormone. TBBPA in the concentration range of 1 x 10(-8) to 1 x 10(-6) M showed suppressive action on T3 (5 x 10(-8) M)-enhancement of Rana rugosa tadpole tail shortening. These facts suggest that TBBPA, TCBPA, TMBPA and DMBPA can act as thyroid hormone-disrupting agents.
authors.affiliation: Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan. skitamu@hiroshima-u.ac.jp
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kitamura
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Kato
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Iida
authors.forename: Norimasa
authors.initials: N
authors.lastname: Jinno
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.forename: Nariaki
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Hanada
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kashiwagi
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D016466:CHO Cells; D002733:Chlorophenols / Q000494:pharmacology; D006224:Cricetinae; D005260:Female; D005411:Flame Retardants / Q000494:pharmacology*; D017930:Genes, Reporter / Q000235:genetics; D007814:Larva; D008675:Metamorphosis, Biological / Q000187:drug effects*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D011898:Ranidae; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000187:drug effects* / Q000235:genetics; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D013956:Antithyroid Agents; D002733:Chlorophenols; D005411:Flame Retardants; D011075:Polybrominated Biphenyls; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; C041181:tetrachlorodian; C020806:tetrabromobisphenol A