Elucidation of the mechanism for the chemical substances such as polychlorinated biphenyls induced decrease in the serum thyroxine level
| Project/Area Number |
18K11660
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 63030:Chemical substance influence on environment-related
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 甲状腺ホルモン撹乱 / サイロキシン / polychlorinated biphenyl / phenobarbital / 肝臓 / グルクロン酸抱合酵素 / ラット / PCB / トランスポーター / マウス / Oatp2 / トランスサイレチン / TTRノックアウトマウス / Kanechlor-500 / 甲状腺ホルモン / 化学物質 |
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| Outline of Final Research Achievements |
The present studies indicate that Kanechlor-500 (KC500)-mediated decrease in serum thyroxine (T4) level occurs in a transthyretin (TTR)-unrelated manner and further suggest that KC500-promoted T4 accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T4 transportation from serum to liver. The present studies demonstrate that the decrease in serum total T4 level by phenobarbital (PB) in Gunn rats is not dependent on the increase in hepatic UDP-glucuronosyltransferase (T4-UDP-GT) activity and suggest that even in Wistar rats, the PB-induced decrease in serum T4 level dose not occur only through increase in hepatic T4-UDP-GT. The present studies suggest that PB-mediated increase in hepatic T4 accumulation occurs, at least in part, through the increase in the expression of hepatic T4-transporters, such as Oatp2.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、ヒトを含む多くの動物種に対する内分泌系への影響が懸念されているPCBおよびフェノバルビタールなどの化学物質の甲状腺ホルモン撹乱作用、特に血中甲状腺ホルモン濃度の低下作用発現に関する新規メカニズムを解明し、T4濃度低下作用メカニズムの本質となるT4の肝臓への蓄積メカニズムの実体解析を試みた点において、学術的に意義深い研究であると考えられる。本研究の成果は、血中甲状腺ホルモン濃度の低下作用を誘発するPCBなどの化学物質の毒性に対する安全性対策、医薬品（フェノバルビタールなど）のリスク評価や副作用の回避に応用できることから社会的に価値ある研究であると考えられる。
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Kanechlor 500-mediated changes in serum and hepatic thyroxine levels primarily occur in a transthyretin-unrelated manner2019
Author(s)
Kato Y, Tamaki S, Haraguchi K, Ikushiro S, Fujii Y, Ohta C, Atobe K, Kimura O, Endo T, Koga N, Yamada S, Degawa M
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Journal Title
Journal of Applied Toxicology
Volume: 39
Issue: 12
Pages: 1701-1709
DOI
Related Report
Peer Reviewed
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[Presentation] In vitro metabolism of 2,2',3,4',5,6,6'-heptachlorobiphenyl (CB188) by rat liver microsomes.2018
Author(s)
Ohta C., Yamamoto K., Fujii Y., Haraguchi K., Kimura O., Endo T., Kato Y., Koga N.
Organizer
38th International Symposium on Halogenated Persistent Organic Pollutants
Related Report
Int'l Joint Research
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