Elucidation of the mechanism for the chemical substances such as polychlorinated biphenyls induced decrease in the serum thyroxine level

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K11660
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63030:Chemical substance influence on environment-related
• Research Institution: Tokushima Bunri University
• Principal Investigator: KATO Yoshihisa 徳島文理大学, 薬学部, 教授 (90161132)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 甲状腺ホルモン撹乱 / サイロキシン / polychlorinated biphenyl / phenobarbital / 肝臓

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.

Free Research Field

薬物の体内動態と薬効・毒性発現メカニズムの解明

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。