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.

Abstract

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.