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
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
复制标题
DOI：
10.1248/bpb.b13-00775
复制
发表时间：
2014-03-01
影响因子：
2
通讯作者：
Degawa, Masakuni
中科院分区：
文献类型：
--
作者：
Kato, Yoshihisa;Haraguchi, Koichi;Degawa, Masakuni
单次腹膜内注射（50毫克/千克）的3，3 '，4，4'-四氯联苯（CB 77），一种2，3，7，8-四氯二苯并-对-二恶英（TCDD）型多氯联苯，TCDD敏感的C57 BL/6和TCDD-2小鼠在给药后7 d血清总甲状腺素（T4）和游离T4水平均显著降低，而血清促甲状腺激素水平无明显升高。DBA/2小鼠。当在CB 77处理后7天向小鼠注射[I-125]T-4时，与相应对照小鼠中的水平相比，C57 BL/6小鼠中胆汁[I-125]T-4和[I-125]T-4-葡糖苷酸的水平在注射后增加90至120 mm，但DBA/2小鼠中未增加。相反，在两种小鼠品系中，CB 77预处理导致与血清甲状腺素运载蛋白、白蛋白和甲状腺素结合球蛋白结合的[I-125]T-4水平发生类似变化。因此，CB 77处理促进了[（125 I）]T-4从血清中的清除，并进一步提高了[I-125]T-4的稳态分布容积、肝脏与血清的浓度比（Kp值）以及[I-125]T-4在两种小鼠品系中的肝脏中的分布。目前的研究结果表明，在小鼠中，CB 77介导的血清T-4水平降低是通过肝脏T-4积累增加而不是通过肝脏甲状腺素-尿苷5 '-二磷酸-葡萄糖醛酸基转移酶活性增加而发生的。
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 (T-4) and free T-4 without increase in the level of serum thyroid-stimulating hormone at 7d later in both TCDD-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. When [I-125]T-4 was injected into the mice 7d after treatment with CB77, the levels of biliary [I-125]T-4 and [I-125]T-4-glucuronide increased 90 to 120 mm 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 [I-125]T-4 bound to the serum transthyretin, albumin, and thyroxine-binding globulin. Consequently, treatment with CB77 promoted the clearance of [(125I)]T-4, from the serum and further raised the steady-state volumes of distribution of [I-125]T-4, the concentration ratio (Kp value) of the liver to the serum, and the distribution of [I-125]T-4 in the liver in both strains of mice. The present findings indicate that in mice, the CB77-mediated decrease in the serum T-4 level occurs through enhanced accumulation of hepatic T-4 rather than through increased activity of hepatic thyroxine-uridine 5'-diphosphate-glucuronosyltransferase(s).