Elucidation of lactation control mechanisms focusing on the Endoplasmic Reticulum stress response in the mammary gland and new approaches to the study of lactation regulation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03126
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42010:Animal production science-related
• Research Institution: Shinshu University
• Principal Investigator: Yonekura Shinichi 信州大学, 学術研究院農学系, 教授 (40443113)
• Co-Investigator(Kenkyū-buntansha): 芳賀 聡 国立研究開発法人農業・食品産業技術総合研究機構, 畜産研究部門, 主任研究員 (90442748) ; 渡邉 敬文 酪農学園大学, 獣医学群, 准教授 (50598216) ; 徳武 優佳子 東北大学, 農学研究科, 助教 (90824657)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 乳腺上皮細胞 / 小胞体ストレス応答 / 小胞体生合成 / 細胞死 / 乳牛

Outline of Final Research Achievements

We focused on the endoplasmic reticulum stress response (UPR) as an intracellular mechanism involved in the lactation ability of mammary epithelial cells. We found that IGF-1 secreted from the liver activates IRE1-XBP1, a pathway of the UPR, to promote endoplasmic reticulum biosynthesis, which is responsible for the expansion of the endoplasmic reticulum (ER) that is associated with increased milk production. On the other hand, cell death, which is responsible for decreased milk production, was found to be induced by saturated fatty acids inducing apoptosis by activating PERK-CHOP, one pathway of the UPR. We also found that severe endoplasmic reticulum stress occurs in the liver of dairy cows when they suffer from energy deficiency, and that 5-aminolevulinic acid feeding, a component of heme, reduces endoplasmic reticulum stress.

Free Research Field

家畜生理学

Academic Significance and Societal Importance of the Research Achievements

乳量増減に関与する細胞内機構と内因性因子を明らかにしたことから、今後、泌乳平準化する技術開発する上で有用な基礎的知見となることが期待される。さらに、本研究で同定した小胞体ストレスを低減する効果を有する５アミノレブリン酸やウルソデオキシコール酸の給与は、泌乳初期の負のエネルギーバランス時に有効である可能性が考えられる。