A Possible Mechanism for the Decrease in Serum Thyroxine Level by a 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Like Polychlorinated Biphenyl Congener, 3,3′,4,4′,5-Pentachlorobiphenyl in Mice

Serum total thyroxine (T 4 ) and free T 4 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 T 4 -UDP-glucuronosyltransferase (T 4 -UGT) were significantly increased in C57BL/6 mice but not in DBA/2 mice. Furthermore, the amounts of biliary [ 125 I]T 4 and [ 125 I]T 4 glucuronide after injection of [ 125 I]T 4 were increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. Clearance of [ 125 I]T 4 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 [ 125 I]T 4 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 [ 125 I]T 4 was increased only in C57BL/6 mice. The present findings indicate that CB126-mediated decrease in serum T 4 occurs through the increase in hepatic T 4 -UGT and the enhanced accumulation of hepatic T 4 along with development of liver hypertrophy.