Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo.
Previous results in experimental systems have suggested that hydroxylated PCBs may decrease thyroid hormone levels through associative interaction with transthyretin. In the present paper it was investigated whether this property was also shared by various industrial chemicals, mainly pesticides. In total, 65 compounds from 12 chemical groups were analyzed for direct interference with the T4 binding site of transthyretin using a competitive binding assay. Sixty per cent of the compounds were competitive at a concentration level of 100 microM. Relatively strong interactions were observed by several chlorophenols, chlorophenoxy acids and nitrophenols, as well as by individual compounds such as hexachlorobenzene, dicofol, bromoxynil and tetrachlorohydroquinone. Examples from these chemical groups, e.g. pentachlorophenol, 2,4-dichlorophenoxybutyric acid, dinoseb and bromoxynil, also reduced plasma TT4 levels in rats. In addition, bromoxynil decreased plasma TT3 levels. The results suggest the existence of a number of halogenated industrial chemicals with a potential for lowering plasma thyroid hormone levels through interference with hormone transport carriers.
Van den Berg
K J
KJ
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
van Raaij
J A
JA
Bragt
P C
PC
Notten
W R
WR
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D008297:Male; D011228:Prealbumin / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood*
D006846:Hydrocarbons, Halogenated; D011228:Prealbumin; D011988:Receptors, Thyroid Hormone; D013974:Thyroxine