Abstract

Serum total thyroxine (T₄) and free T₄ levels were markedly decreased 7 days after treatment with 3,3′,4,4′,5-pentachlorobiphenyl (CB126) (2.5 mg/kg i.p.) in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 mice but not in TCDD-resistant DBA/2 mice. At the same time, the level and activity of hepatic T₄-UDP-glucuronosyltransferase (T₄-UGT) were significantly increased in C57BL/6 mice but not in DBA/2 mice. Furthermore, the amounts of biliary [¹²⁵I]T₄ and [¹²⁵I]T₄ glucuronide after injection of [¹²⁵I]T₄ were increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. Clearance of [¹²⁵I]T₄ from serum was also promoted by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. On the other hand, no significant changes in the steady-state volumes of distribution of [¹²⁵I]T₄ and in the concentration ratio (K_p value) of the liver to serum by CB126 pretreatment were observed in either strain of mice. Because liver weight was increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice, hepatic total [¹²⁵I]T₄ was increased only in C57BL/6 mice. The present findings indicate that CB126-mediated decrease in serum T₄ occurs through the increase in hepatic T₄-UGT and the enhanced accumulation of hepatic T₄ along with development of liver hypertrophy.