title: A possible mechanism for 2,3',4,4',5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level in mice.
abstract: The effect of 2,3',4,4',5'-pentachlorobiphenyl (CB118) on serum total thyroxine (T₄) level was comparatively examined between C57BL/6 and DBA/2 mice, which are sensitive and insensitive, respectively, to aryl hydrocarbon receptor-mediated biological changes. After 5 d of CB118 administration (50 mg/kg, intraperitoneally (i.p.)), the serum total T₄ levels in both strains of mice were markedly decreased. However, significant decreases in serum thyroid-stimulating hormone levels were observed in DBA/2 mice, but not in C57BL/6 mice. In contrast, significant increases in the level and activity of hepatic T₄-uridine 5'-diphosphate (UDP)-glucuronosyltransferase by CB118 treatment were observed only in C57BL/6 mice. Likewise, significant increases in the amounts of biliary [(125)I]T₄ and [(125)I]T₄-glucuronide after injection of [(125)I]T4 were observed only in the CB118-pretreated C57BL/6 mice. The CB118-mediated changes in the levels of [(125)I]T₄ bound to transthyretin (TTR), albumin, and thyroxine binding globulin (TBG) were also observed in C57BL/6 mice, but not in DBA/2 mice. Despite such strain differences, significant increases in the liver-selective accumulation of [(125)I]T₄ by CB118-pretreatment was observed in both C57BL/6 and DBA/2 mice. The present findings indicate that CB118-mediated decreases in levels of serum T₄ in C57BL/6 and DBA/2 mice occur mainly through enhanced accumulation of hepatic T₄.
authors.affiliation: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University.
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: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects*; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D011228:Prealbumin / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood* / Q000378:metabolism; D056825:Thyroxine-Binding Globulin / Q000378:metabolism; D014530:Uridine Diphosphate / Q000378:metabolism
chemical_list: D000418:Albumins; D004785:Environmental Pollutants; D011228:Prealbumin; D056825:Thyroxine-Binding Globulin; C070055:2,3',4,4',5-pentachlorobiphenyl; D014530:Uridine Diphosphate; D013972:Thyrotropin; D011078:Polychlorinated Biphenyls; D014453:Glucuronosyltransferase; D013974:Thyroxine