RT Journal Article
SR Electronic
T1 4-Hydroxy-2,2′,3,4′,5,5′,6-heptachlorobiphenyl-Mediated Decrease in Serum Thyroxine Level in Mice Occurs through Increase in Accumulation of Thyroxine in the Liver
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 2095
OP 2102
DO 10.1124/dmd.109.028621
VO 37
IS 10
A1 Yoshihisa Kato
A1 Koichi Haraguchi
A1 Makiko Kubota
A1 Yoshiki Seto
A1 Shin-ichi Ikushiro
A1 Toshiyuki Sakaki
A1 Nobuyuki Koga
A1 Shizuo Yamada
A1 Masakuni Degawa
YR 2009
UL http://dmd.aspetjournals.org/content/37/10/2095.abstract
AB 4-Hydroxy-2,2′,3,4′,5,5′,6-heptachlorobiphenyl (4-OH-CB187) was selected as a major hydroxylated polychlorinated biphenyl metabolite detected from serum of wildlife and humans and was examined for its effect on level of serum thyroid hormone in mice. Four days after treatment of C57BL/6 and DBA/2 mice with 4-OH-CB187 (1.0 mg/kg), the serum total thyroxine (T4) and free T4 levels were decreased in both strains of mice. On the other hand, no significant changes in the level and activity of the T4-UDP-glucuronosyltransferases, including UGT1a and UGT1a1, by the 4-OH-CB187 treatment were observed in either strain of mice. No 4-OH-CB187-mediated change in level of serum thyroid-stimulating hormone was observed in either strain of mice. Binding levels of [125I]T4 to serum proteins after administration of [125I]T4 were significantly changed in 4-OH-CB187-pretreated mice: a decrease in the level of serum [125I]T4-transthyretin (TTR) complex and an increase in the binding level of [125I]T4 to serum albumin and thyroxine binding protein in both strains of mice. Clearance from serum of T4 was promoted by 4-OH-CB187 pretreatment in both C57BL/6 and DBA/2 mice, and the levels of T4 in several tissues, especially the liver, were increased. In addition, 4-OH-CB187-mediated decreases in serum total T4 and free T4 levels were observed in wild-type and TTR-heterozygous mice but not in TTR-deficient mice. The present findings show that 4-OH-CB187 shows a definite ability to decrease serum T4 level and further indicate that the 4-OH-CB187-induced decrease would occur through increase in accumulation of T4 in the liver. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics