Comparative study on 2,2',4,5,5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice

摘要

The relationships between the changes in the levels of serum total thyroxine (T 4), serum T 4-transthyretin (TTR) complex, and accumulation of T 4 in tissues by 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T 4 was much higher in WT mice than in TTR-null mice. In WT mice 4days after a single intraperitoneal injection with PentaCB (112mg/kg), serum total T 4 level was significantly decreased along with a decrease in serum T 4-TTR complex, and the levels of serum total T 4 in the PentaCB-treated WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T 4 by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [ 125I]T 4 from the serum after [ 125I]T 4-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [ 125I]T 4 in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [ 125I]T 4 and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T 4 level occurs mainly through increase in accumulation level of T 4 in the liver and further indicate that the increased accumulation of T 4 in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T 4-TTR complex formation.