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.

Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, Japan.
Drug metabolism and disposition: the biological fate of chemicals (Impact Factor: 3.74). 09/2009; 38(1):150-6. DOI: 10.1124/dmd.109.029348
Source: PubMed

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.

  • Womens Studies International Forum - WOMEN STUD INT FORUM. 01/2001; 24(3):482-483.
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    ABSTRACT: Serum total thyroxine (T₄) level was markedly decreased, without significant increases in the levels of hepatic T₄-UDP-glucuronosyltransferase (T₄-UGT) and serum thyroid-stimulating hormone, 3 days after treatment with 2,2',4,4',5,5'-hexachlorobiphenyl (CB153) (100mg/kg, ip) in both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. Likewise, in either strain of mice, no CB153-mediated changes in the binding levels of [(125)I]T₄ to serum proteins, such as transthyretin, albumin, and thyroxine binding globulin, were observed, while in CB153-pretreated C57BL/6 mice, but not in CB153-pretreated DBA/2 mice, the levels of biliary [(125)I]₄T and [(125)I]T₄-glucuronide at 90-120 min after injection of [(125)I]T₄ slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [(125)I]T₄, liver-selective increases in the [(125)I]T₄ accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [(125)I]T₄ in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [(125)I]T₄ dosed, respectively. The present findings indicated that the CB153-mediated decreases in the level of serum total T₄in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T₄ in the liver.
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