The effects of environmental chemicals on thyroid hormone systems during the critical period of developing cerebellum

• Project/Area Number: 16K00557
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Gunma University
• Principal Investigator: Miyazaki Wataru 群馬大学, 大学院医学系研究科, 准教授 (90512278)
• Research Collaborator: Amano Izuki ; Haijima Asahi ; Koibuchi Noriyuki ; Hollenberg Anthony N
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 環境化学物質 / 甲状腺ホルモン / 脳発達 / 小脳 / 内分泌攪乱 / 甲状腺ホルモン受容体

Outline of Final Research Achievements

Thyroid hormone (TH) and the systems have important roles on brain development including cerebellum. However, the mechanisms of several adverse effects on the development by environmental chemicals are still unclear. In this study, to clarify the mechanisms, we focused on the interaction between TH receptors (TRs) and TH response elements (TREs) during the critical period of developing cerebellum.
To identify the TREs which were responsible for the expression of target genes on cerebellum development, we performed chromatin immune precipitation assay with anti-TR antibodies. In addition, microarray analysis was performed to realize the target genes induced or suppressed by TH stimulation during the critical period.
These results may be one of the important information to clarify the mechanism.

Academic Significance and Societal Importance of the Research Achievements

本研究では、小脳の発達において、甲状腺ホルモン（TH）の刺激によって大きく発現が変動する遺伝子群を明らかにするとともに、その中でも特に化学物質によって異常な変化が引き起こされる可能性のあるものを同定した。
これらの結果はヒトの脳発達に重要な甲状腺ホルモン（TH）系の役割の解明につながり、さらに環境化学物質によるヒトへの影響を防ぐ上で必要不可欠な基礎データである。

Research Products

• [Journal Article] A possible novel mechanism of action of genistein and daidzein for activating thyroid hormone receptor (TR)-mediated transcription (2018)
  • Author(s): Ariyani Winda、Iwasaki Toshiharu、Miyazaki Wataru、Lu Yu、Takeda Shigeki、Koibuchi Noriyuki
  • Journal Title: Toxicological Sciences Volume: 印刷中 Issue: 2 Pages: 417-427
  • DOI: 10.1093/toxsci/kfy097
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis. (2016)
  • Author(s): Ariyani W, Iwasaki T, Miyazaki W, Khongorzul E, Nakajima T, Kameo S, Koyama H, Tsushima Y, Koibuchi N.
  • Journal Title: Front Endocrinol Volume: 7 Pages: 1-11
  • DOI: 10.3389/fendo.2016.00115
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] The Changes of Thyroid Hormone Receptors (TRs)-mediated Transcription by Direct Binding of Isoflavones to TRs In Vitro (2018)
  • Author(s): Wataru Miyazaki, Winda Ariyani, Toshiharu Iwasaki, Noriyuki Koibuchi
  • Organizer: ENDO 2018, the Endocrine Society's annual meeting
  • Int'l Joint Research
• [Presentation] 甲状腺ホルモン受容体を介するArntの発現制御 (2018)
  • Author(s): 宮崎航、岩崎俊晴、鯉淵典之
  • Organizer: 日本生理学会 第95回大会
• [Presentation] 甲状腺ホルモン受容体を介する転写に対するArntの関与 (2017)
  • Author(s): 宮崎航、岩崎俊晴、鯉淵典之
  • Organizer: 日本生理学会 第94回大会
  • Place of Presentation: 浜松アクトシティコングレスセンター、浜松
  • Year and Date: 2017-03-28
• [Presentation] Arntの転写発現における甲状腺ホルモン受容体の関与 (2017)
  • Author(s): 宮崎航、岩崎俊晴、鯉淵典之
  • Organizer: 日本内分泌かく乱化学物質学会 第20回研究発表会
• [Presentation] 肝臓における甲状腺ホルモン受容体を介する転写におけるArntの関与 (2016)
  • Author(s): 宮崎航、岩崎俊晴、鯉淵典之
  • Organizer: 日本内分泌かく乱化学物質学会 第19回研究発表会
  • Place of Presentation: 文部科学省研究交流センター、つくば
  • Year and Date: 2016-12-08