The different effects of anti-thyroid drugs on regulation of NIS and other gene expressions that play key role on thyroid function

• Project/Area Number: 26860713
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Toho University
• Principal Investigator: SUE Mariko 東邦大学, 医学部, 助教 (50439965)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 甲状腺機能 / 抗甲状腺薬

Outline of Final Research Achievements

6-propyl-2-thiouracil (PTU) and 2-mercapto-1-methilimidazole (MMI) are widely used curatives for Graves` disease. Instead of the similar anti-thyroid effects, their molecular structure and mechanism of actions are different. We have previously reported that PTU strongly increased NIS mRNA and protein expressions in the absence of TSH. In this research we revealed a few genes either induced or suppressed under PTU or MMI stimulation in the cells cultured with TSH, including Dehal1 and MCT8 that play key role in thyroid hormone synthesis through Iodine-recycling. The inhibitory effect of PTU on Dehal1 gene and protein expressions were observed only in the cells cultured with TSH, where as that of MMI was independent of TSH stimulation. Interestingly, Dehal1 gene expression was induced by TSH, Insulin or Serum stimulation, where as Iodine stimulation had inhibitory effect.

Research Products

• [Journal Article] Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes. (2017)
  • Author(s): Oda K, Luo Y, Yoshihara A, Ishido Y, Sekihata K, Usukura K, Sue M, Hiroi N, Hirose T, Suzuki K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 483 Issue: 1 Pages: 541-546
  • DOI: 10.1016/j.bbrc.2016.12.109
  • Peer Reviewed / Open Access
• [Journal Article] A Novel Role for Flotillin-Containing Lipid Rafts in Negative-Feedback Regulation of Thyroid-Specific Gene Expression by Thyroglobulin. (2016)
  • Author(s): Luo Y, Akama T, Okayama A, Yoshihara A, Sue M, Oda K, Hayashi M, Ishido Y, Hirano H, Hiroi N, Katoh R, Suzuki K.
  • Journal Title: Thyroid Volume: 26 Issue: 11 Pages: 1630-1639
  • DOI: 10.1089/thy.2016.0187
  • Peer Reviewed / Open Access
• [Presentation] Different effects of PTU and MMI on thyroid-specific gene expression (2015)
  • Author(s): 吉原彩、須江麻里子、小田健三郎、石藤雄子、Luo Yuqian、廣井直樹、鈴木幸一
  • Organizer: 15th International Thyroid Congress
  • Place of Presentation: フロリダ（アメリカ合衆国）
  • Year and Date: 2015-10-21
  • Int'l Joint Research