Species differences among mice, hamsters, rats and guinea pigs in PCB-induced alteration of serum thyroid hormone level
Species differences among mice, hamsters, rats and guinea pigs in PCB-induced alteration of serum thyroid hormone level
批准号:
15510058
负责人:
KATO Yoshihisa
金额:
$2.18万
依托单位:
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
项目状态:
已结题
起止时间:
2003 至 2005
中文摘要
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
英文摘要
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
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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:
--
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)。
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
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
DOI:
--
发表时间:
2003
期刊:
Organohalogen Compd. 64
影响因子:
--
作者:
[Inoue T, Igarashi K, Sekizawa J, Yoshihisa Kato]
通讯作者:
Yoshihisa Kato
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。
DOI:
--
发表时间:
2004
期刊:
Organohalogen Compd. 66
影响因子:
--
作者:
[Hayashi, T., Inoue T, Nobuyuki Koga]
通讯作者:
Nobuyuki Koga
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
共 40 条
Elucidation of the mechanism for the chemical substances such as polychlorinated biphenyls induced decrease in the serum thyroxine level
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批准号:18K11660
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.91万
-
财政年份:2018
-
负责人:KATO Yoshihisa
-
依托单位:
Study on the exact mechanism for the polychlorinated biphenyl-induced decrease in the serum thyroxine level
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批准号:23510083
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项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$3.49万
-
财政年份:2011
-
负责人:KATO Yoshihisa
-
依托单位:
Chemical oceanographic section study of dissolved barium in the western Indian Ocean
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批准号:22510018
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.66万
-
财政年份:2010
-
负责人:KATO Yoshihisa
-
依托单位:
Latitudinal section mapping of pore water constituents in the central and eastern equatorial Pacific
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批准号:19510014
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项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.91万
-
财政年份:2007
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负责人:KATO Yoshihisa
-
依托单位:
A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls
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批准号:18510061
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项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.71万
-
财政年份:2006
-
负责人:KATO Yoshihisa
-
依托单位:
Development of Ba-Si/N diagram in the ocean
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批准号:15510010
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$1.6万
-
财政年份:2003
-
负责人:KATO Yoshihisa
-
依托单位:
Methylsulfonyl metabolites of polychlorinated biphenyl and polybrominated biphenyl as disrupters of endocrine action
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批准号:12680549
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.43万
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财政年份:2000
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负责人:KATO Yoshihisa
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依托单位:
Comparative paleoceanographical study using piston cores from Okhotsk Basin and Suiko Sea Mount
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批准号:11640491
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.24万
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财政年份:1999
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负责人:KATO Yoshihisa
-
依托单位:
The role of 3-methylsulfony (3-MeSOィイD22ィエD2) metabolites in the induction of hepatic microsomal drug-metabolizing enzymes by PCB congeners, and the toxicological effects of the MeSOィイD22ィエD2 metabolites of PCB congeners
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批准号:09680531
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.05万
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财政年份:1997
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负责人:KATO Yoshihisa
-
依托单位:
北西太平洋における海洋古環境の観測タワーとしての孤立海山の利用とその検証
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批准号:09640586
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$1.73万
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财政年份:1997
-
负责人:KATO Yoshihisa
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依托单位:
海外基金