A possible mechanism for 2,2′,4,4′,5,5′-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice

Serum total thyroxine (T4) level was markedly decreased, without significant increases in the levels of hepatic T4–UDP-glucuronosyltransferase (T4–UGT) and serum thyroid-stimulating hormone, 3 days after treatment with 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB153) (100 mg/kg, ip) in both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. Likewise, in either strain of mice, no CB153-mediated changes in the binding levels of [125I]T4 to serum proteins, such as transthyretin, albumin, and thyroxine binding globulin, were observed, while in CB153-pretreated C57BL/6 mice, but not in CB153-pretreated DBA/2 mice, the levels of biliary [125I]T4 and [125I]T4–glucuronide at 90–120 min after injection of [125I]T4 slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [125I]T4, liver-selective increases in the [125I]T4 accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [125I]T4 in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [125I]T4 dosed, respectively. The present findings indicated that the CB153-mediated decreases in the level of serum total T4 in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T4 in the liver.