Species differences among mice, hamsters, rats and guinea pigs in PCB-induced alteration of serum thyroid hormone level

PCB引起的血清甲状腺激素水平改变中小鼠、仓鼠、大鼠和豚鼠的物种差异

• 批准号: 15510058
• 负责人: KATO Yoshihisa
• 金额: $ 2.18万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15510058/
• 关键词: polychlorinated biphenyl; endocrine-disrupter; species difference; thyroid hormone; UDP-glucuronosyltransferase; tranthyretin; liver; transporter; グルクロン酸抱合体; マウス; ラット; ハムスター; モルモット; サイロキシイン

In the present study, we investigated the mechanism for the decrease in levels of serum thyroid hormones, especially thyroxine (T_4), by polychlorinated biphenyls (PCBs) such as Kanechlor-500 (KC500),2,2',4',5,5'-pentachlorobiphenyl (PentaCB), and 2,2',3',4',5,6-hexachlorobiphenyl (HexaCB), and studied species difference among mice, hamsters, rats, and guinea pigs in the PCB effect. Significant decrease in serum total T_4 level by KC500 was observed in all four species. On the other hand, there were differences in the level of decrease of serum total T_4 level by PentaCB and HexaCB. Differences in the level of hepatic methylsulfonyl-PCB and OH-PCB metabolites of KC500, PentaCB and HexaCB, which were thought to be associated with the PCB-toxic effects, did not necessarily correlate with the magnitude of decrease in serum total T_4 level. Likewise, the induction of CYP1A, CYP2B, CYP3A, iodothyronine deiodinase and UDP-glucuronosyltransferases (T_4-UDP-GT) toward T_4 by PCB did not necess … More arily correlate with the decrease in serum T_4 level in the animals used. In addition, the PCB-mediated decrease in serum total T_4 level in UGT1A-deficient Wistar rats (Gunn rats) occurred without an increase in hepatic T_4-UDP-GT activity. Further studies on transthyretin (TTR) and serum T_4-transpoter suggested that decrease in serum total T_4 level by PCB occurred not only by induction of T_4-UDP-GT but also by the alteration of levels of T_4-TTR binding and hepatic T_4-transporter. In addition, species difference in the decrease of serum total T_4 level was associated with various PCB-induced total effects, including induction of T_4-UDP-GT, decrease in T_4-TTR binding level, the increase of hepatic thyroid hormone transporter, and other thyroid function correlates. In conclusion, the present findings suggest that in the animals used, the PCB-induced decrease in serum T_4 level dose not occur only through increase in hepatic T_4-UDP-GT, and further suggest that in all four species, the PCB-mediated decrease occurs through the increased transportation of T_4 to the liver. Furthermore, the decrease in the binding of T_4 to serum TTR and hepatic hyperplasia might be attributed to the increase in the level of T_4 in the liver. Further studies are necessary for understanding the susceptibility toward a PCB-mediated decrease in serum T_4 level in animals including humans. Less

本研究探讨了多氯联苯（PCBs）如kanechor -500 （KC500）、2,2‘、4’、5,5‘-五氯联苯（PentaCB）和2,2’、3‘、4’、5,6-六氯联苯（HexaCB）对血清甲状腺激素尤其是甲状腺素（T_4）水平的影响机制，并研究了PCBs对小鼠、仓鼠、大鼠和豚鼠的影响。KC500显著降低了4种动物的血清总T_4水平。另一方面，PentaCB与HexaCB对血清总T_4水平的降低程度存在差异。肝脏甲基磺酰多氯联苯和oh -多氯联苯代谢物KC500、PentaCB和HexaCB的水平差异被认为与多氯联苯毒性作用有关，但与血清总T_4水平下降的幅度并不一定相关。同样，多氯联苯对CYP1A、CYP2B、CYP3A、碘甲状腺原氨酸脱碘酶和udp -葡萄糖醛酸基转移酶（T_4- udp - gt）向T_4的诱导作用也不是必需的，更多的是与使用动物血清T_4水平的降低相关。此外，多氯联苯介导的ugt1a缺陷Wistar大鼠（Gunn大鼠）血清总T_4水平的降低发生在没有增加肝脏T_4- udp - gt活性的情况下。进一步对甲状腺转甲状腺素（TTR）和血清T_4转座蛋白的研究表明，PCB降低血清总T_4水平不仅通过诱导T_4- udp - gt，还通过改变T_4-TTR结合和肝脏T_4转运蛋白的水平。此外，血清总T_4水平降低的物种差异与pcb诱导的各种总效应有关，包括T_4- udp - gt的诱导、T_4- ttr结合水平的降低、肝甲状腺激素转运体的增加等甲状腺功能相关。总之，目前的研究结果表明，在使用的动物中，多氯联苯诱导的血清T_4水平的降低并不仅仅通过肝脏T_4- udp - gt的增加而发生，并且进一步表明，在所有四种动物中，多氯联苯介导的降低都是通过增加T_4到肝脏的运输而发生的。此外，T_4与血清TTR结合的减少和肝脏增生可能归因于肝脏中T_4水平的增加。需要进一步的研究来了解对多氯联苯介导的血清T_4水平降低的易感性，包括人类在内的动物。少

项目成果

In vitro metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) with liver microsomes of rats, hamsters and guinea pigs.

大鼠、仓鼠和豚鼠肝微粒体对 2,2,3,4,5,5,6-七氯联苯 (CB187) 的体外代谢。

• 发表时间: 2004
• 期刊: Organohalogen Compd. 66
• 作者: Hayashi;T.;Inoue T;Nobuyuki Koga
• 通讯作者: Nobuyuki Koga

Species difference among mice, hamsters, rats and guinea pigs in 2,2',4',5,5'-pentachlorobiphenyl and 2,2',3',4',5,6-hexachlorobiphenyl-induced alterations of serum thyroid hormone level

小鼠、仓鼠、大鼠和豚鼠2,2,4,5,5-五氯联苯和2,2,3,4,5,6-六氯联苯诱导的血清甲状腺激素变化的物种差异

• 发表时间: 2003
• 期刊: Organohalogen Compd. 64
• 作者: Inoue T;Igarashi K;Sekizawa J;Yoshihisa Kato
• 通讯作者: Yoshihisa Kato

Polychlorinated biphenylsによる血中サイロキシン濃度低下作用機構

多氯联苯降低血甲状腺素浓度的作用机制

• 发表时间: 2004
• 期刊: Endocrine Disrupter News Letter 7
• 作者: Koichi Haraguchi;Chiho Ohta;Makiko Kubota;Rie Takiguchi;Kelly J.Gauger;Yoshihisa Kato;加藤善久
• 通讯作者: 加藤善久

古賀信幸: "2、3、3'、4、4'-五塩素化ビフェニル(CB105)のハムスターにおける代謝"福岡医学雑誌. 94. 174-182 (2003)

Nobuyuki Koga：“仓鼠中 2,3,3,4,4-五氯联苯 (CB105) 的代谢”福冈医学杂志 94. 174-182 (2003)。

A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats

• DOI: 10.1093/toxsci/kfh225
• 发表时间: 2004-10-01
• 期刊: TOXICOLOGICAL SCIENCES
• 影响因子: 3.8
• 作者: Kato, Y;Ikushiro, S;Degawa, M
• 通讯作者: Degawa, M