Molecular mechanisms of negative feedback regulation of hypothalamo-pituitary-adrenal axis

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Suzuka University of Medical Science (2020-2023); Kochi University (2019)
• Principal Investigator: Iwasaki Yasumasa 鈴鹿医療科学大学, 保健衛生学部, 教授 (30303613)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: プロオピオメラノコルチン / ストレス / ネガティブフィードバック / グルココルチコイド / 下垂体

Outline of Final Research Achievements

We investigated the molecular mechanisms underlying the negative feedback regulation of the hypothalamo-pituitary-adrenal (HPA) axis using hypothalamic and pituitary cells in vitro. We found that FKBP4 and 5, as well as HDAC6 regulate binding affinity between glucocorticoid hormone receptor and its chaperone molecule (HSP90), whereas GDF15 is induced by glucocorticoid and involved in both CRH and POMC gene transcription. These bioactive molecules may be future targets for the development of anti-stress medicine.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

視床下部・下垂体・副腎軸によるストレスホルモン分泌制御機構の解明は、ストレス過多の社会における重要な研究領域である。今回の研究で対象となった生理活性物質は、今後の抗ストレス薬の治療標的となる可能性があり、創薬への応用が期待される。