The molecular mechanism of the linear-log relation between thyrotropin synthesis and T3

• Project/Area Number: 24590689
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SASAKI Shigekazu 浜松医科大学, 医学部附属病院, 講師 (20303547)
• Co-Investigator(Kenkyū-buntansha): MATSUSHITA Akio 浜松医科大学, 医学部附属病院, 助教 (50402269)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 甲状腺刺激ホルモン / 甲状腺ホルモン / 転写因子 / 甲状腺ホルモン受容体 / GATA2 / ネガティブフィードバック / 下垂体 / 副腎皮質刺激ホルモン / thyrotropin / thyroid hormone / transcription / TRH

Outline of Final Research Achievements

There is a linear-log relationship between the syntheses of thyroid-stimulating hormone (TSH) in pituitary and serum thyroid hormone (T3, T4) as in the case between the adrenocorticotropic hormone and glucocorticoid.　　Based on our tethering model where transactivating function of transcription factor GATA2, which is essential for the TSHbeta expression, is interfered with by T3 in the presence of its receptor (TR), we have studied the role of T3-bound TRbeta 2 in the transcriptional auto-regulation of the GATA2 gene. Our current results may provide the insight for the expression of the TSHbeta gene which is negatively regulated by T3 with linear-log relationship.

Research Products

• [Journal Article] Essential Role of TEA Domain Transcription Factors in the Negative Regulation of the MYH 7 Gene by Thyroid Hormone and Its Receptors. (2014)
  • Author(s): Iwaki H, Sasaki S, Matsushita A, Ohba K, Matsunaga H, Misawa H, Oki Y, Ishizuka K, Nakamura H, Suda T.
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] Non-islet cell tumor-induced hypoglycemia associated with macronodular pulmonary metastases from poorly differentiated thyroid carcinoma. (2014)
  • Author(s): Morioka T, Ohba K, Morita H, Takahashi G, Uchida H, Matsushita A, Sasaki S, Oki Y, Suda T, Kakudo K, Yoshino A.
  • Journal Title: Thyroid Volume: 24 Pages: 395-399
  • Peer Reviewed
• [Journal Article] A sudden onset and the spontaneous remission of severe hypo-high-density lipoprotein cholesterolemia without serious underlying disease: a case report. (2013)
  • Author(s): Ohba K, Oki Y, Fujita K, Kameko F, Moriyama T, Horiike Y, Morita H, Matsushita A, Iino K, Sasaki S, Nakamura H, Maekawa M.
  • Journal Title: Clin Chim Acta Volume: 15 Pages: 91-94
  • Peer Reviewed
• [Journal Article] Factors associated with fluorine-18-fluorodeoxyglucose uptake in benign thyroid nodules. (2013)
  • Author(s): Ohba K, Sasaki S, Oki Y, Nishizawa S, Matsushita A, Yoshino A, Suda T, Nakamura H.
  • Journal Title: Endocr J Volume: 60 Pages: 985-90
  • NAID: 10031195768
  • Peer Reviewed
• [Journal Article] Inappropriate elevation of serum thyrotropin levels in patients treated with axitinib. (2013)
  • Author(s): Ohba K, Takayama T, Matsunaga H, Matsushita A, Sasaki S, Oki Y, Ozono S, Nakamura H.
  • Journal Title: Thyroid Volume: 23 Pages: 443-448
  • Peer Reviewed
• [Presentation] TSHβの発現をT3がリニア・ログの様式で負に調節する機序の解明-in-vitro再構成系を用いた検討 (2017)
  • Author(s): 平原直子
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2017-04-23
• [Presentation] T3-bound TR inhibits the expression of transcription factor GATA2, which is the key activator for the TSHÎβ gene (2013)
  • Author(s): Shigekazu Sasaki, Hiroko Misawa Nakamura, Akio Matsushita, Hideyuki Matsunaga,Yutaka Oki
  • Organizer: Endocrine Society's 95th Annual Meeting
  • Place of Presentation: San Francisco
• [Presentation] preproTRH遺伝子における転写因子GATA2ならびにT3受容体β２の作用 (2013)
  • Author(s): 佐々木茂和、三沢啓子、松下明生、大場健司、松永英之、沖隆
  • Organizer: 第86回日本内分泌学会
  • Place of Presentation: 仙台
• [Presentation] T3-bound TR inhibits the expression of transcription factor GATA2, which is the key activator for the TSHβ gene (2013)
  • Author(s): Shigekazu Sasaki, Hiroko Misawa Nakamura, Akio Matsushita, Kenji Ohba, Hideyuki Matsunaga et al.
  • Organizer: The Endocrine Society's 95th Annual Meeting & Expo
  • Place of Presentation: San Francisco
• [Remarks] 浜松医科大学内分泌代謝内科
  • URL: http://www.hamamatsu-endo.com/sinryoka/group.html