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2017 Fiscal Year Final Research Report

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

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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
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
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.

Free Research Field

内分泌学

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Published: 2019-03-29  

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