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Regulation of glucose metabolism by estrogen and its implication on evolution of reproductive strategies

Research Project

Project/Area Number 20K15835
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44040:Morphology and anatomical structure-related
Research InstitutionTokyo University of Science

Principal Investigator

Genki Yamagishi  東京理科大学, 先進工学部生命システム工学科, 研究員 (80845868)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsエストロゲン / 卵生 / 胎生 / 糖新生 / 爬虫類 / 遺伝子重複 / 卵巣サイクル / 卵胞発育 / 排卵 / g6pc1 / 糖代謝 / 遺伝子発現 / 脂肪合成 / 胎生魚
Outline of Research at the Start

エストロゲンは繁殖中の栄養動員をになうが、卵生と胎生の動物で血糖値を逆向きに制御する。このことは、胎生移行にともなう栄養動員機構の再編成を示唆する。しかし、卵生動物で栄養動員を引き起こすしくみは不明である。本研究ではニホンヤモリを用いてエストロゲンの代謝制御を遺伝子発現と代謝物から解析するとともに、遺伝子ノックダウン実験でも検証する。また、胎生移行による再編成を非哺乳類の胎生種で調べる。

Outline of Final Research Achievements

Estrogen has regulatory roles on glucose metabolism. However, significance of such regulation on reproduction is currently unclear. This research investigated the mechanisms through which estrogen regulates metabolism in reproducing vertebrates. This study used geckos as a model to study oviparous vertebrates. In the liver of female geckos, the expression of key gluconeogenic genes were repressed throughout reproductive period. This observation suggests lowered gluconeogenesis in reproducing females. Geckos were also found to possess two duplicated g6pc1 genes. Expression of these genes were differently regulated by estrogen. Such difference may aid in energy partitioning between reproduction and maternal survival. In viviparous fish, which was used as a viviparous vertebrate model, estrogen-insensitive gluconeogenic pathways were found. Such pathway may help reproducing females to provide embryos with glucose, because it can synthesize glucose under increased blood estrogen levels.

Academic Significance and Societal Importance of the Research Achievements

本研究では、卵生脊椎動物の糖新生が繁殖中を通じて低下することを明らかにした。また、そのような糖新生活性の低下を補償するしくみの存在を示唆する結果を得た。これにより、エストロゲンによる繁殖中代謝の動態を明らかにした。同時に、胎生への移行に伴って新たな代謝経路が獲得された可能性を示し、卵生―胎生という繁殖戦略によりエネルギー代謝制御機構が変化することを明らかにした。以上を通じ、エストロゲンによる糖新生制御の進化的意義解明に道筋をつけた。さらに本研究の社会的意義として、卵生脊椎動物の繁殖中代謝を解明することで、人間の食糧として重要な水産魚種や鶏といった動物種の効率的な養殖法開発への応用が考えられる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Neuroendocrinology of Reproduction and Social Behaviors in Reptiles: Advances Made in the Last Decade.2023

    • Author(s)
      Genki Yamagishi, Shinichi Miyagawa
    • Journal Title

      Zoological Science

      Volume: 41 Issue: 1 Pages: 87-96

    • DOI

      10.2108/zs230060

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phylogeny of g6pc1 Genes and Their Functional Divergence among Sarcopterygian Vertebrates: Implications for Thermoregulatory Strategies.2022

    • Author(s)
      Genki Yamagishi, Min Kyun Park, Shinichi Miyagawa
    • Journal Title

      Zoological Science

      Volume: 39 Issue: 5 Pages: 419-430

    • DOI

      10.2108/zs210113

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] 胎生魚ハイランドカープのエストロゲン非依存的な繁殖中代謝2023

    • Author(s)
      山岸弦記、宮川信一
    • Organizer
      第47回日本比較内分泌学会大会及びシンポジウム 九州大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 卵生動物におけるエストロゲン応答性の糖代謝制御の検証2022

    • Author(s)
      山岸弦記、宮川信一
    • Organizer
      第46回日本比較内分泌学会大会及びシンポジウム
    • Related Report
      2022 Research-status Report
  • [Presentation] 羊膜類の糖新生酵素g6pc1の遺伝子重複とその生理学的意義の解明2021

    • Author(s)
      山岸弦記、朴民根、宮川信一
    • Organizer
      第45回日本比較内分泌学会大会
    • Related Report
      2021 Research-status Report
  • [Book] Epigenetic Regulation of Sex Determination and Toxicity in Non-mammalian Vertebrates. In: Genomic and Epigenomic Biomarkers of Toxicology and Disease: Clinical and Therapeutic Actions.2022

    • Author(s)
      Genki Yamagishi, Taisen Iguchi, Shinichi Miyagawa
    • Total Pages
      512
    • Publisher
      John Wiley & Sons Ltd
    • ISBN
      9781119807704
    • Related Report
      2022 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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