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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

基本信息

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

项目摘要

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Kanechlor-500（KC 500）、2，2 '，4'，5，5 '-五氯联苯（PentaCB）和2，2'，3 '，4'，5，6-六氯联苯（HexaCB）引起血清甲状腺激素，尤其是甲状腺素（T_4）水平下降的机制，并研究了小鼠、仓鼠、大鼠、和豚鼠的PCB效应。用KC 500测定血清总T_4含量，结果表明，四种鱼血清总T_4含量均显著降低。PentaCB和HexaCB对血清总T_4水平的降低程度存在差异。KC 500、PentaCB和HexaCB的肝甲磺酰-PCB和OH-PCB代谢物水平的差异被认为与PCB的毒性效应有关，但与血清总T_4水平的降低幅度无关。同样，PCB对CYP 1A、CYP 2B、CYP 3A、碘甲腺原氨酸脱碘酶和UDP-葡萄糖醛酸转移酶（T_4-UDP-GT）向T_4的诱导作用也不是必需的。 ...更多信息与所用动物血清T_4水平的降低有关。此外，在UGT 1A缺陷的Wistar大鼠（古恩大鼠）中，PCB介导的血清总T_4水平的降低并不引起肝脏T_4-UDP-GT活性的升高。对甲状腺素运载蛋白（transthyretin，TTR）和血清T_4-转运体的进一步研究表明，PCB引起血清总T_4水平的降低不仅是通过诱导T_4-UDP-GT，而且还通过改变T_4-TTR结合水平和肝脏T_4-转运体水平。此外，血清T_4水平降低的种属差异与多氯联苯引起的多种总体效应有关，包括T_4-UDP-GT的诱导、T_4-TTR结合水平的降低、肝脏甲状腺激素转运体的增加以及其他甲状腺功能相关因素。以上结果提示，在所用动物中，多氯联苯引起的血清T_4水平的降低不是仅仅通过增加肝脏T_4-UDP-GT而发生的，而且在所有四种动物中，多氯联苯引起的血清T_4水平的降低都是通过增加T_4向肝脏的转运而发生的。T_4与血清TTR结合的降低和肝脏增生可能与肝脏T_4水平升高有关。对多氯联苯引起的动物（包括人）血清T_4水平降低的易感性还需进一步研究。少

项目成果

期刊论文数量（90）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

DOI：
发表时间：
2004
期刊：
Endocrine Disrupter News Letter 7
影响因子：
0
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)。