The mechanism of cyclic activity of GnRH neurons causing ovulation and follicle maturation.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06924
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Watanabe Miho 浜松医科大学, 医学部, 助教 (10399321)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: GABA / GnRHニューロン / CRHニューロン / クロライド / 生殖 / 視床下部

Outline of Final Research Achievements

The mechanisms that reduced nutritional status affects the activity of GnRH neurons involved in reproductive regulation and CRH neurons involved in the stress response were investigated. Food restriction to mice disrupted intracellular chloride homeostasis of CRH neurons and weakened inhibitory GABAergic input, which increased the activity of CRH neurons and activated the hypothalamic-pituitary-adrenal axis, thereby affecting the activity of GnRH neurons. I also examined whether synchronization of GnRH neuron activity is a mechanism for the cyclic or pulsatile secretion of GnRH neurons.

Free Research Field

神経内分泌学

Academic Significance and Societal Importance of the Research Achievements

栄養状態の低下による体重の減少などにより、視床下部-下垂体の機能が低下し、無月経や無排卵になる中枢性排卵障害が知られているが、本研究で栄養状態の低下が細胞内クロライドホメオスタシスに影響を及ぼし、GABAによる神経活動制御に変化をもたらすことが、生殖機能低下のメカニズムの一端であることを明らかになり、細胞内ホメオスタシスを維持するトランスポーターやトランスポーターの活動を制御する分子を対象とした新たな治療法の開発につながると考える。