Mechanism of secretory rhythm generation of GnRH that regulates mammalian reproduction.

• Project/Area Number: 19K15961
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42010:Animal production science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Murata Ken 東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (30749643)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: GnRH / キスペプチン / 生殖制御 / 神経トレーシング / 透明化 / 性周期 / GnRHパルスジェネレーター / GnRHサージジェネレーター

Outline of Research at the Start

哺乳類の雌の性周期は、性腺刺激ホルモン放出ホルモン（GnRH）のパルス状分泌およびサージ状分泌によって制御されることが知られているが、それらのリズム形成機構についてはよくわかっていない。本研究では、in vivo Ca2+イメージング法、トランスシナプストレーシング法、薬理遺伝学的手法を組み合わせることで、パルスおよびサージリズムがどのような神経回路で、どのようなメカニズムによって形成されるのかを明らかにする。

Outline of Final Research Achievements

The mammalian reproductive endocrine system is regulated by the secretory rhythm of GnRH, which is thought to be regulated by kisspeptin neurons in the hypothalamic arcuate nucleus. To investigate the mechanism of pulse generation/modulation based on neural circuits, we comprehensively investigated the input to the kisspeptin neurons using mono-trans-synaptic retrograde tracing and brain transparency techniques. We found that input was received primarily from the hypothalamus, but also from a number of neuronal nuclei throughout the forebrain and brainstem, with some slight sexual dimorphism. These results will contribute to the future elucidation of the mechanisms of GnRH pulse generation and regulation.

Academic Significance and Societal Importance of the Research Achievements

哺乳類の生殖を制御するGnRHの分泌メカニズムは、生殖生物学における重要な課題である。近年、その分泌リズムを制御する視床下部弓状核キスペプチン神経が見つかり、この神経を活性化、抑制するペプチドなども見つかってきたが、神経回路レベルでの理解は進んでいない。この神経への入力を網羅的に調べた本研究はその足がかりとなると考えられる。また、この理解が進むことにより、不妊治療や生殖制御技術の開発にも繋がる可能性がある。

Research Products

• [Journal Article] Hemoglobin in the blood acts as a chemosensory signal via the mouse vomeronasal system (2022)
  • Author(s): Osakada T, Abe T, Itakura T, Mori H, Ishii KK, Eguchi R, Murata K, Saito K, Haga-Yamanaka S, Kimoto H, Yoshihara Y, Miyamichi K, Touhara K.
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 556-556
  • DOI: 10.1038/s41467-022-28118-w
  • Peer Reviewed / Open Access
• [Journal Article] CUBIC-Cloud provides an integrative computational framework toward community-driven whole-mouse-brain mapping (2021)
  • Author(s): Mano T, Murata K, Kon K, Shimizu C, Ono H, Shi S, Yamada RG, Miyamichi K, Susaki EA, Touhara K, Ueda HR.
  • Journal Title: Cell Reports Methods Volume: 1 Issue: 2 Pages: 100038-100038
  • DOI: 10.1016/j.crmeth.2021.100038
  • Peer Reviewed / Open Access
• [Journal Article] Origin and evolution of the gene family of proteinaceous pheromones, the exocrine gland-secreting peptides, in rodents. (2021)
  • Author(s): Niimura Y, Tsunoda M, Kato S, Murata K, Yanagawa T, Suzuki S, Touhara K
  • Journal Title: Mol Biol Evol Volume: 38 Issue: 2 Pages: 634-649
  • DOI: 10.1093/molbev/msaa220
  • Peer Reviewed / Open Access
• [Journal Article] Hypothalamic Neuronal Circuits Regulating Hunger-Induced Taste Modification (2019)
  • Author(s): Fu O, Iwai Y, Narukawa M, Ishikawa AW, Ishii KK, Murata K, Yoshimura Y, Touhara K, Misaka T, Minokoshi Y, Nakajima KI.
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 4560-4560
  • DOI: 10.1038/s41467-019-12478-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Contribution of Individual Olfactory Receptors to Odor-Induced Attractive or Aversive Behavior in Mice (2019)
  • Author(s): Horio N, Murata K, Yoshikawa K, Yoshihara Y, Touhara K.
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 209-209
  • DOI: 10.1038/s41467-018-07940-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 雄マウスプライマーフェロモンの探索 (2021)
  • Author(s): 村田健
  • Organizer: Chemosensation and Behavior Workshop 2020
• [Presentation] Analysis of primer pheromone in mice: ligand to the central action (2019)
  • Author(s): Ken Murata, Sayoko Ihara, Kazunari Miyamichi, Kazushige Touhara
  • Organizer: The 48th Naito Conference
  • Int'l Joint Research