GATA2 Mediates the Negative Regulation of the Prepro-Thyrotropin-Releasing Hormone Gene by Liganded T3 Receptor beta2 in the Paraventricular Nucleus of the Hypothalamus.
| Project/Area Number |
15K09425
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松下 明生 浜松医科大学, 医学部附属病院, 助教 (50402269)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(8 results)
