Central regulatory system of reproduction by neuropeptides including kisspeptin.

• Project/Area Number: 24570067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphology/Structure
• Research Institution: St. Marianna University School of Medicine (2015); The University of Tokyo (2012-2014)
• Principal Investigator: Akazome Yasuhisa 聖マリアンナ医科大学, 医学部, 講師 (50302807)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: キスペプチン / ニューロペプチドFF / NPFF / GPR74 / GPR147 / kiss1 / kiss2 / メダカ / NPFF受容体 / GnRH / 自己・傍分泌 / シグナル伝達 / NPFFR2 / GPF74 / プロテインキナーゼA / 終神経 / GPR54

Outline of Final Research Achievements

Kisspeptin plays pivotal roles in reproduction in mammals. However, its functions in non-mammalian species remain enigmatic. I therefore analyzed signal transduction of medaka (Olyzias latipes) GPR74, which reportedly receives kisspeptin in human, and GPR147, which share common ligands (NPFF/RFRP) with GPR74. At low concentrations, NPFF or RFRP reduced forskolin-induced CRE-luciferase activity in HEK293T cells expressing GPR74/GPR147 . However, at higher concentrations, NPFF/RFRP increased CRE-luciferase activity in these cells. Such a concentration-dependent biphasic responsiveness of GPR74/GPR147 to ligands may suggest that medaka GPR74 and GPR147 have an intrinsic ability of maintaining the cellular response within a certain range.

Research Products

• [Journal Article] Morphological analysis of the early development of telencephalic and diencephalic gonadotropin-releasing hormone neuronal systems in the enhanced green fluorescent protein-expressing transgenic medaka lines. (2016)
  • Author(s): Takahashi A, Islam MS, Abe H, Okubo K, Akazome Y, Kaneko T, Hioki H, *Oka Y.
  • Journal Title: J Comp Neurol Volume: 524 Issue: 4 Pages: 896-913
  • DOI: 10.1002/cne.23883
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic evolution of the GnRH receptor gene family in vertebrates. (2014)
  • Author(s): Williams, BL. Akazome, Y., Oka, Y. and Eisthen, H.L.
  • Journal Title: BMC Evolutionary Biology. Volume: 14 Issue: 1 Pages: 215-215
  • DOI: 10.1186/s12862-014-0215-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Kiss1 neurons drastically change their firing activity in accordance with the reproductive state: insights from a seasonal breeder. (2014)
  • Author(s): Hasebe M, Kanda S, Shimada H, Akazome Y, Abe H, Oka Y.
  • Journal Title: Endocrinology Volume: 155 Issue: 12 Pages: 4868-4880
  • DOI: 10.1210/en.2014-1472
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anatomical distribution of sex steroid hormone receptors in the brain of female medaka. (2013)
  • Author(s): Buntaro Zempo, Shiaji Kanda, Kataaki Okubo, Yasuhisa Akazome and Yshitaka Oka.
  • Journal Title: The Journal of Comparative Neurology Volume: 521(8) Issue: 8 Pages: 1760-80
  • DOI: 10.1002/cne.23255
  • Peer Reviewed
• [Journal Article] Neuroanatomical evidence that kisspeptin directly regulates isotocin and vasotocin neurons (2013)
  • Author(s): Kanda, S., Akazome, Y., Mitani, Y., Okubo, K., and Oka, Y.
  • Journal Title: PLosOne Volume: 8 Issue: 4 Pages: e62776-e62776
  • DOI: 10.1371/journal.pone.0062776
  • Peer Reviewed
• [Presentation] Ligand dose-dependent switch in G-protein coupling (Gi and Gs) of medaka (Oryzias latipes) neuropeptide FF receptors, NPFFR1 (GPR147) and NPFFR2 (GPR74) (2015)
  • Author(s): Yasuhisa Akazome, Eri Yamamoto, Yoshitaka Oka
  • Organizer: ENDO2015 (The Endocrine Society's 97th Annual Meeting & Expo)
  • Place of Presentation: サンディエゴ（米国）
  • Year and Date: 2015-03-07
• [Presentation] Functional analysis of kisspeptin neuronal system in teleosts using knockout medaka (2015)
  • Author(s): Akiko Takahashi, Shinji Kanda, Yasuhisa Akazome, Yoshitaka Oka
  • Organizer: ENDO2015 (The Endocrine Society's 97th Annual Meeting & Expo)
  • Place of Presentation: サンディエゴ（米国）
  • Year and Date: 2015-03-06
• [Presentation] POA ER alpha neurons transmit estrogen fedback signal to GnRH1 neurons for the hypothalamo-pituitary-gonadal axis regulation (2015)
  • Author(s): Buntaro Zempo, Shinji Kanda, Yasuhisa Akazome, Yoshitaka Oka
  • Organizer: ENDO2015 (The Endocrine Society's 97th Annual Meeting & Expo)
  • Place of Presentation: サンディエゴ（米国）
  • Year and Date: 2015-03-06
• [Presentation] The ovary as an origin of female sex pheromonal substances in medaka. (2014)
  • Author(s): Yuki Mori, Buntaro Zempo, Shinji Kanda, Yasuhisa Akazome, Yoshitaka Oka
  • Organizer: 第20回小型魚類研究会
  • Place of Presentation: 慶應義塾大学（東京都）
  • Year and Date: 2014-09-20 – 2014-09-21
• [Presentation] メダカ脳におけるエストロジェン受容体α発現ニューロンの可視化および神経線維投射の形態学的解析 (2014)
  • Author(s): 善方文太郎、神田真司、赤染康久、岡 良隆
  • Organizer: 日本動物学会第85回大会
  • Place of Presentation: 東北大学（宮城県仙台市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Morphological analysis of the early development of GnRH neuron systems (2013)
  • Author(s): Takahashi, A., Islam, S., Akazome, Y., Abe, H., Okubo, K., Oka, Y.
  • Organizer: The 43th Annual Meeting of theSociety for Neuroscience
  • Place of Presentation: San Diego, United States
• [Presentation] Kiss2 may activate receptors for neuropeptide FF (NPFF)/ RFamide related peptide (RFRP) in medaka (2012)
  • Author(s): Akazome, Y., Yamamoto, E., Oka, Y.
  • Organizer: Second World Conference of Kisspeptin Signaling in the Brain
  • Place of Presentation: 東京、東京大学伊藤国際学術研究センター