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.

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We have studied the glucuronidation of the thyroid hormones T4, T, and rT, by liver microsomes of Wistar, Gunn and WAG rats. Gunn rats have a defect in the gene coding for bilirubin and phenol UDP-glucuronyltransferase (UGT) isoenzymes; WAG rats have a genetic defect in androsterone UGT. In normal Wistar rats UGT activity was &fold higher for rT> than for T, or T,. UGT activities for T4 and rT,, but not for T,, were impaired in Gunn rats. Conversely, UGT activity for T,, but not for T, or rT,, was impaired in WAG rats. Thus, in rat liver rT, is glucuronidated much more rapidly than T, and T,. Our results support the view that T, and rT, are glucuronidated by bilirubin and phenol UGTs and T, by androsterone UGT.

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