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

Abstract

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) (100mg/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 [(125)I]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 [(125)I]₄T and [(125)I]T₄-glucuronide at 90-120 min after injection of [(125)I]T₄ slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [(125)I]T₄, liver-selective increases in the [(125)I]T₄ accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [(125)I]T₄ in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [(125)I]T₄ dosed, respectively. The present findings indicated that the CB153-mediated decreases in the level of serum total T₄in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T₄ in the liver.