Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors.

摘要

We examined the effects of industrial, medical and agricultural chemicals on 3,5,3'-L-[125I]triiodothyronine ([125I]T(3)) binding to transthyretins (TTRs) and thyroid hormone receptors (TRs). Among the chemicals investigated diethylstilbestrol (DES) was the most powerful inhibitor of [125I]T(3) binding to chicken and bullfrog TTR (cTTR and bTTR). Inhibition of [125I]T(3) binding was more apparent in cTTR than bTTR. Scatchard analysis revealed DES, pentachlorophenol and ioxynil as competitive inhibitors of [125I]T(3) binding to cTTR and bTTR. However, cTTR's affinity for the three chemicals was higher than its affinity for T(3). A miticide dicofol (10(-10)-10(-7) M) activated [125I]T(3) binding to bTTR up to 170%. However, at 4x10(-5) M it inhibited [125I]T(3) binding by 83%. Dicofol's biphasic effect upon [125I]T(3) binding was not detected in TTRs from other species. DES and pentachlorophenol, in the presence of plasma, increased cellular uptake of [125I]T(3) in vitro, by displacing [125I]T(3) from its plasma binding sites. These chemicals did not, however, affect the association of cTTR with chicken retinol-binding protein. All chemicals investigated had little or no influence on [125I]T(3) binding to chicken TR (cTR) and bullfrog TR (bTR). Several endocrine disrupting chemicals that were tested interfered with T(3) binding to TTR rather than to TR. Binding of the endocrine disrupting chemicals to TTR may weaken their intrinsic effects on target cells by depressing their free concentrations in plasma. However, this may affect TH homeostasis in vivo by altering the free concentrations of plasma THs.