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

作者：Kato Yoshihisa^*; Haraguchi Koichi; Kubota Makiko; Seto Yoshiki; Okura Takashi; Ikushiro Shin ichi; Koga Nobuyuki; Yamada Shizuo; Degawa Masakuni

来源：Drug Metabolism and Disposition, 2010, 38(1): 150-156.

DOI：10.1124/dmd.109.029348

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 [I-125] T-4 and [I-125] T-4 glucuronide after injection of [I-125] T-4 were increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. Clearance of [I-125] 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 [125I] 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 [I-125] 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.

• 出版日期2010-1