Thyroid hormonal activity of the flame retardants tetrabromobisphenol A and tetrachlorobisphenol A.
The thyroid hormonal-disrupting activity of the flame retardants tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) was examined and compared with that of bisphenol A, a typical estrogenic xenobiotic. TBBPA and TCBPA, halogenated derivatives of bisphenol A, markedly inhibited the binding of triiodothyronine (T(3); 1 x 10(-10) M) to thyroid hormone receptor in the concentration range of 1 x 10(-6) to 1 x 10(-4) M, but bisphenol A did not. The thyroid hormonal activity of TBBPA and TCBPA was also examined using rat pituitary cell line GH3 cells, which grow and release growth hormone (GH) depending on thyroid hormone. TBBPA and TCBPA enhanced the proliferation of GH3 cells and stimulated their production of GH in the concentration range of 1 x 10(-6) to 1 x 10(-4) M, while bisphenol A was inactive. TBBPA, TCBPA, and bisphenol A did not show antagonistic action, i.e., these compounds did not inhibit the hormonal activity of T(3) to induce growth and GH production of GH3 cells. TBBPA and TCBPA, as well as bisphenol A, enhanced the proliferation of MtT/E-2 cells, whose growth is estrogen-dependent. These results suggest that TBBPA and TCBPA act as thyroid hormone agonists, as well as estrogens.
Kitamura
Shigeyuki
S
School of Medicine, Institute of Pharmaceutical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. skitamu@hiroshima-u.ac.jp
Jinno
Norimasa
N
Ohta
Shigeru
S
Kuroki
Hiroaki
H
Fujimoto
Nariaki
N
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002733:Chlorophenols / Q000494:pharmacology*; D005411:Flame Retardants / Q000494:pharmacology*; D007700:Kinetics; D010902:Pituitary Gland; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D002733:Chlorophenols; D005411:Flame Retardants; D011075:Polybrominated Biphenyls; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C041181:tetrachlorodian; C020806:tetrabromobisphenol A