The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor

We investigated the effect of endocrine disrupting chemicals (EDCs), including medical, industrial, and agricultural chemicals, on 3,3',5-L-[I-125]triiodothyronine ([I-125]T-3) binding to purified Japanese quail transthyretin (qTTR), a major thyroid hormone-binding protein in plasma, and to the ligand-binding domain of thyroid hormone receptor beta (qTR LBD). Scatchard plots of T-3 binding to qTTR and qTR LBD revealed two classes of binding sites, with K-d values of 6.9 and 185 nM, and a single class of binding sites, with K-d value of 0.31 nM, respectively. Among the test chemicals, diethylstilbestrol was the most powerful inhibitor of [I-125]T-3 binding to qTTR (IC50<0.4nM). Diethylstilbestrol, ioxynil (IC50 = 1.1 +/- 0.5nM) and pentachlorophenol (IC50 = 6.3 +/- 3.8nM) displaced [I-125]T-3 from qTTR more effectively than unlabeled T-3 (IC50 = 9.7 +/- 0.9 nM) did. Although malathion, 4-nonylphenol, bisphenol A and n-butylbenzyl phthalate were effective inhibitors of [I-125]T-3 binding to qTTR, their potency was two orders of magnitude less than that of T-3. All test chemicals except for diethylstilbestrol had either a weak or no effect on [I-125]T-3 binding to qTR LBD. These results show that several EDCs tested in this study target qTTR rather than qTR LBD. (C) 2003 Elsevier Science (USA). All rights reserved.