The Effects of Endocrine-Disrupting Chemicals on Thyroid Hormone Binding to Xenopus laevis Transthyretin and Thyroid Hormone Receptor

Abstract

We investigated the effects of medical, industrial and agricultural chemicals on 3,3′,5-L-[¹²⁵I]triiodothyronine ([¹²⁵I]T₃) binding to purified recombinant Xenopus laevis (X. laevis) transthyretin (xTTR), a plasma thyroid hormone-binding protein, and to the ligand-binding domain of thyroid hormone receptor-β (xTR LBD). xTTR derived from X. laevis serum had about 80 times higher affinity for T₃ than for L-thyroxine. The xTTR's relative affinities for diethylstilbestrol, pentachlorophenol and ioxynil were 10⁻¹- to 10⁻²-fold less than that for T₃. However, all chemicals investigated had either a weak or no influence on [¹²⁵I]T₃ binding to xTR LBD. The concentration of diethylstilbestrol, the most potent chemical, required for 50% inhibition of [¹²⁵I]T₃ binding to xTR LBD was 10⁴ times greater than that of unlabeled T₃. These results indicate the existence of several chemicals that interact with xTTR but not with xTR LBD.