title: A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice.
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.
authors.affiliation: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, Japan. kato@kph.bunri-u.ac.jp
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kato
authors.forename: Mao
authors.initials: M
authors.lastname: Onishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikushiro
authors.forename: Chiho
authors.initials: C
authors.lastname: Ohta
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koga
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Endo
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Masakuni
authors.initials: M
authors.lastname: Degawa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000037:antagonists & inhibitors / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D013974:Thyroxine; C014024:2,4,5,2',4',5'-hexachlorobiphenyl