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GATA2 Mediates the Negative Regulation of the Prepro-Thyrotropin-Releasing Hormone Gene by Liganded T3 Receptor beta2 in the Paraventricular Nucleus of the Hypothalamus.

Research Project

Project/Area Number 15K09425
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionHamamatsu 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) 松下 明生  浜松医科大学, 医学部附属病院, 助教 (50402269)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords甲状腺刺激ホルモン放出ホルモン / 甲状腺刺激ホルモン / 甲状腺ホルモン / 甲状腺ホルモン受容体 / GATA2 / 下垂体 / 視床下部 / 転写 / TRH / T3受容体 / 転写調節 / TSH
Outline of Final Research Achievements

T3 inhibits thyrotropin-releasing hormone (TRH) in hypothalamus. Although T3 receptor (TR) β2 is known to mediate the negative regulation of prepro-TRH gene, its mechanism is unknown. We previously studied the T3-dependent negative regulation of the thyrotropin β subunit (TSHβ) gene, and reported that T3-bound TRβ2 inhibits the function of transcription factor GATA2, which is essential for TSHβ expression. Here, we found the expression of GATA2 in the TRH neuron by immunostaining. Using CAT reporter assay, we found that the promoter is activated by GATA2 approximately 6-fold. We identified a functional GATA-responsive element (nt. -357 and nt. -352). When TRβ2 was co-expressed, T3 reduced GATA2-dependent promoter activity to approximately 30%. The negative regulation of prepro-TRH gene was maintained even after the mutation of so called negative T3 responsive element. Thus, the prepro-TRH gene may be negatively regulate by the mechanism common to the TSHβ gene.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016

All Journal Article (1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] The Mechanism of Negative Transcriptional Regulation by Thyroid Hormone: Lessons From the Thyrotropin β Subunit Gene.2018

    • Author(s)
      Sasaki S, Matsushita A, Kuroda G, Nakamura HM, Oki Y, Suda T.
    • Journal Title

      Vitam Horm

      Volume: 106 Pages: 97-127

    • DOI

      10.1016/bs.vh.2017.06.006

    • ISBN
      9780128141168
    • Related Report
      2017 Annual Research Report
  • [Presentation] GATA2 Mediates the Negative Regulation of the Prepro-Thyrotropin-Releasing Hormone Gene by Liganded T3 Receptor β2 in the Paraventricular Nucleus of the Hypothalamus.2018

    • Author(s)
      Kuroda G, Sasaki S, Matsushita A, Nakamura H, Oki Y
    • Organizer
      2018年米国内分泌学会(ENDO2018)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 甲状腺ホルモンによる負の転写調節:視床下部と下垂体に共通な分子機構は存在するか?2018

    • Author(s)
      黒田豪、佐々木茂和、松下明生、酒井勇輝、中村啓子、沖隆
    • Organizer
      第91回日本内分泌学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] prepro-TRH遺伝子のT3によるネガティブフィードバック機構には転写因子GATA2が関与する2017

    • Author(s)
      黒田豪、佐々木茂和、松下明生、平原直子、三沢啓子、沖隆
    • Organizer
      第90回日本内分泌学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2017-04-20
    • Related Report
      2016 Research-status Report
  • [Presentation] The Role of GATA2 in the Negative Regulation of the Prepro- Thyrotropin-Releasing Hormone Gene By Liganded T3 Receptor Beta 22017

    • Author(s)
      Kuroda G, Sasaki S, Matsushita A, Nakamura H, Yamashita M, Oki Y
    • Organizer
      2017年米国内分泌学会(ENDO2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] prepro-TRH遺伝子のT3によるネガティブフィードバック機構には転写因子GATA2が関与する2017

    • Author(s)
      黒田豪、佐々木茂和、松下明生、平原直子、中村啓子、沖隆
    • Organizer
      第90回日本内分泌学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 転写因子GATA2はT3によるprepro-TRH遺伝子への負の調節を媒介する2016

    • Author(s)
      黒田豪、佐々木茂和、松下明生、平原直子、三沢啓子、沖隆
    • Organizer
      第59 回日本甲状腺学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] T3によるpreproTRH遺伝子への負の調節における転写因子GATA2の意義2016

    • Author(s)
      黒田 豪、佐々木 茂和、松下 明生 、 平原 直子、三沢 啓子 、沖 隆
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2016-04-21
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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