Relationship between lutenization function and Calpastatin

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K20167
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: International University of Health and Welfare (2018); St. Marianna University School of Medicine (2015-2017)
• Principal Investigator: Kawashima Ikko 国際医療福祉大学, 医学部, 研究員 (40633946)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 黄体化 / 更年期障害 / 排卵 / Calpain / 顆粒層細胞 / Calpastatin / カルシウム

Outline of Final Research Achievements

Our study suggested that luteinization requires the activity of Calpain at 5.5 hours after LH stimulation. It was found that when Calpain activity in Granulosa cells was inhibited during luteinization, luteal cells did not become normal progesterone-producing cells but became Estrogen-producing cells. Since this is a phenotype observed in the early stage of the menopausal disorder, We considered that Calpain activity decreased early in menopause. And our considered that calpastatin, as endogenous calpain inhibitor, was blocked calpain activation. The expression of Calpastatin was detected in aged mice and young mice, and it was clarified that it was predominantly high in aged mice. Furthermore, another group showed that the Calpain 1/2 knockout mice had normal fertility. Therefore, Calpain family (Calpain 1/2 and more) activation induced luteinization from granulosa cells and overexpression of Calpastatin in aged mice may block luteinization.

Free Research Field

生殖内分泌

Academic Significance and Societal Importance of the Research Achievements

LH刺激による黄体化は、遺伝子発現によって制御を受けていることが知られていたが、タンパク質の活性が、その細胞の分化を制御していることを示唆することができた。さらに、更年期障害の初期でみられるエストロジェン過多を誘発する可能性が示唆される知見が得られ、排卵刺激後のどの時間でそのイベントが発生しうるかを示すことができた。現在、どのCalpainが重要な機能を示しているかを検証する必要はあるが、更年期障害を緩和するための新たな分子標的が明らかとなったことに社会的意義がある。