title: 3,3',4,4'-Tetrachlorobiphenyl-mediated decrease of serum thyroxine level in C57BL/6 and DBA/2 mice occurs mainly through enhanced accumulation of thyroxine in the liver.
abstract: A single intraperitoneal injection (50 mg/kg) of 3,3',4,4'-tetrachlorobiphenyl (CB77), a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-type polychlorinated biphenyl, led to significant decreases in the levels of serum total thyroxine (T4) and free T4 without increase in the level of serum thyroid-stimulating hormone at 7 d later in both TCDD-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. When [(125)I]T4 was injected into the mice 7 d after treatment with CB77, the levels of biliary [(125)I]T4 and [(125)I]T4-glucuronide increased 90 to 120 min post injection in C57BL/6 mice, but not in DBA/2 mice, compared with levels in the corresponding control mice. In contrast, in both strains of mice, the CB77-pretreatment led to similar changes in the levels of the [(125)I]T4 bound to the serum transthyretin, albumin, and thyroxine-binding globulin. Consequently, treatment with CB77 promoted the clearance of [(125)I]T4 from the serum and further raised the steady-state volumes of distribution of [(125)I]T4, the concentration ratio (Kp value) of the liver to the serum, and the distribution of [(125)I]T4 in the liver in both strains of mice. The present findings indicate that in mice, the CB77-mediated decrease in the serum T4 level occurs through enhanced accumulation of hepatic T4 rather than through increased activity of hepatic thyroxine-uridine 5'-diphosphate-glucuronosyltransferase(s).
authors.affiliation: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kato
authors.forename: Koichi
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Mao
authors.initials: M
authors.lastname: Onishi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikushiro
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Endo
authors.forename: Chiho
authors.initials: C
authors.lastname: Ohta
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koga
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Masakuni
authors.initials: M
authors.lastname: Degawa
mesh_terms: D000818:Animals; D020719:Glucuronides / Q000378:metabolism; 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 / Q000494:pharmacology*; D013974:Thyroxine / Q000097:blood / Q000378:metabolism*
chemical_list: D020719:Glucuronides; D011078:Polychlorinated Biphenyls; D014453:Glucuronosyltransferase; D013974:Thyroxine; C028451:3,4,3',4'-tetrachlorobiphenyl