2021 Fiscal Year Final Research Report
Investigation of molecular mechanisms of negative feedback system of HPA axis in central and peripheral tissues
| Project/Area Number |
19K17973
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 視床下部 / 下垂体 / 副腎 / ストレス応答 |
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| Outline of Final Research Achievements |
Using in vitro gene transfer and cell biological techniques with pituitary ACTH-producing AtT20 cells, we analyzed the factors and mechanisms that may influence the negative feedback mechanism of the hypothalamus-pituitary-adrenal (HPA) system.
FKBP4 is directly involved in the negative feedback of glucocorticoids (GCs), and FKBP5 may contribute to the attenuation of the inhibitory effect of GCs on POMC expression via inhibition of the receptor transport. We reported the mechanism in the literature(Int J Mol Sci. 2021 27;22:5724.). GDF15, its transcriptional activity and mRNA expression were attenuated by GC treatment, and knockdown of GDF15 attenuated the inhibitory effect of GC on POMC expression.
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| Free Research Field |
内分泌代謝内科学
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| Academic Significance and Societal Importance of the Research Achievements |
FKBP4、FKBP5がGCのPOMC発現抑制作用において寄与するメカニズムを解明することができた。またその作用機序について、文献報告を行った（Int J Mol Sci. 2021 27;22:5724）。
加えてGDF15の転写活性機構の一部を確認し、下垂体由来ACTH産生AtT20細胞においてその受容体であるGFRALを同定した。これは同蛋白が下垂体ACTH産生細胞におけるフィードバック機構への重要な役割を果たすことを示唆するものと考えられた。これは生体のストレス応答や恒常性維持に重要な役割を果たしている、視床下部-下垂体-副腎（HPA）系の分子学的機構の解明の一助となる。
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