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Hypothalamic hypogonadism: Elucidation of the mechanisms controlling GnRH neural activity via Toll-like receptor 4

Research Project

Project/Area Number 16K20218
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Fujioka Hitomi  聖マリアンナ医科大学, 医学部, 講師 (50410064)

Research Collaborator AKEMA Tatsuo  
FUNABASHI Toshiya  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsGnRH / macrophage / LPS / LH / ストレス / 機能性視床下部性性腺機能低下 / 視床下部性性腺機能低下 / 神経内分泌 / 生植生理学
Outline of Final Research Achievements

Inflammatory/immune challenge is known to suppress LH secretion. We previously discovered that the pretreatment with minocycline (Mino), a potent inhibitor of microglia activation, significantly alleviate the suppression of ovarian steroid-induced LH surge by lipopolysaccharide (LPS) in ovariectomized rats. We also found that Mino suppressed LPS induced interleukin 1β (IL-1β) expression in macrophage in the OVLT. In the present study, we examined distribution of IL-1 receptor in the preoptic area/OVLT, and found IL-1 receptor mRNA located in some vascular structure but not GnRH neurons. Next, we examined whether kiss1 neurons were involved in suppression of LH surge by LPS. We found LPS treatment decreased c-Fos expression in both the kiss1 and GnRH neurons at the peak time of LH surge, that was ameliorated by Mino pretreatment. These results suggest IL-1β induced by LPS suppress GnRH neural activity indirectly through depression of activity in the kiss-1 neurons.

Academic Significance and Societal Importance of the Research Achievements

機能的な視床下部性性腺機能低下はストレスと関連があることが知られている。本研究は、感染ストレスをモデルとして、脳内の免疫担当細胞を介したLHサージ状分泌抑制メカニズムの解明を目指し、その一端を明らかにした。近年、ストレスにより、脳内の免疫担当細胞の活性化が示されていることから、今回の研究の結果は、感染ストレスモデルを超えて、ストレスによる機能的な視床下部性性腺機能低下にも、共通するメカニズムである可能性が考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2018 2017 2016

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

  • [Journal Article] Prostaglandin E2 modulates presynaptic regulation of GnRH neurons via EP4 receptors in accordance with estrogen milieu2017

    • Author(s)
      Fujioka H, Funabashi T, Akema T
    • Journal Title

      Neuroscience

      Volume: 360 Pages: 139-145

    • DOI

      10.1016/j.neuroscience.2017.07.025

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] LPS急性ストレスによるGnRHサージ発生機構の活動抑制とミノサイクリン前投与による抑制解除へのkiss1ニューロンの関与2018

    • Author(s)
      藤岡仁美、舩橋利也、明間立雄
    • Organizer
      日本神経内分泌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 雌ラットにおけるプロスタグランジンE2のGnRHニューロン微小EPSCへの影響2017

    • Author(s)
      藤岡仁美、舩橋利也、明間立雄
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松、静岡県浜松市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] リポポリサッカライドによるLHサージ状分泌抑制に関与する終板脈絡器官のIL-1β産生細胞の特徴2016

    • Author(s)
      藤岡仁美、福島篤、舩橋利也、明間立雄
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜、神奈川県横浜市
    • Year and Date
      2016-07-27
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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