The binding and apoptosis inhibitory action to germ cells of relaxin-like peptide expressed in the boar testis

• Project/Area Number: 24580408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied animal science
• Research Institution: Shizuoka University
• Principal Investigator: KOHSAKA Tetsuya 静岡大学, (連合)農学研究科(研究院), 教授 (10186611)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: relaxin / INSL3 / LGR8 / germ cells / Apoptosis / testis / RLF/INSL3 / 能動免疫 / 造精細胞 / apoptosis / 精巣 / 受容体LGR8 / 造精機能

Outline of Final Research Achievements

This study succeeded in developing a reliable immunoassay for measuring boar relaxin (RXN)-like peptide using a TR-FIA platform and demonstrated that circulating RXN-like peptide concentrations increased progressively in boar during sexual development. Additionally, RXN-like peptide secreted from Leydig cells showed to be transported into the seminiferous compartments at sufficient concentrations. RXN-like peptide revealed to bind with high affinity to, and activates its specific receptor, 85 kDa LGR8/RXFP2, which is expressed in boar meiotic and postmeiotic germ cells. Furthermore, the present study demonstrated that neutralization of RXN-like peptide led to increased germ cell apoptosis and substantially reduced sperm concentration, suggesting that RXN-like peptide functions as a germ cell anti-apoptotic factor in maintaining sperm production.

Research Products

• [Journal Article] The Insulin-Like Factor 3 (INSL3)-Receptor (RXFP2) Network Functions as a Germ Cell Survival/Anti-Apoptotic Factor in Boar Testes. (2015)
  • Author(s): Sagata D, Minagawa I, Kohriki H, Pitia AM, Uera N, Katakura Y, Sukigara H, Terada K, Shibata M, Park EY, Hasegawa Y, Sasada H, Kohsaka T.
  • Journal Title: Endocrinology Volume: 156 Issue: 4 Pages: 1523-1539
  • DOI: 10.1210/en.2014-1473
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective effects of relaxin against cisplatin-induced nephrotoxicity in rats. (2014)
  • Author(s): Yoshida T, Kumagai H, Kohsaka T, Ikegaya N.
  • Journal Title: Nephron Exp Nephrol. Volume: 128 Issue: 1-2 Pages: 9-20
  • DOI: 10.1159/000365852
  • Peer Reviewed / Open Access
• [Journal Article] Dynamics of insulin-like factor 3 and its receptor expression in boar testes. (2014)
  • Author(s): Minagawa I, Sagata D, Pitia AM, Kohriki H, Shibata M, Sasada H, Hasegawa Y, Kohsaka T
  • Journal Title: J Endocrinol. Volume: 220 Issue: 3 Pages: 247-261
  • DOI: 10.1530/joe-13-0430
  • Peer Reviewed
• [Journal Article] The active form of goat insulin-like peptide 3 (INSL3) is a single-chain structure comprising three domains B-C-A, constitutively expressed and secreted by testicular Leydig cells. (2013)
  • Author(s): Siqin, Minagawa I, Okuno M, Yamada K, Sugawara Y, Nagura Y, Hamano K, Park EY, Sasada H, Kohsaka T
  • Journal Title: Biol Chem Volume: 394 Issue: 9 Pages: 1181-1194
  • DOI: 10.1515/hsz-2012-0357
  • Peer Reviewed
• [Journal Article] Expression and localization of RLF/ INSL3 receptor RXFP2 in boar testes. (2013)
  • Author(s): Kohsaka T, Sagata D, Minagawa I, Kohriki H, Pitia AM, Sugii Y, Morimoto M, Uera N, Shibata M, Sasada H, Hasegawa Y.
  • Journal Title: Ital J Anat Embryol Volume: 118 Pages: 23-25
  • Peer Reviewed
• [Journal Article] Relaxin protects against renal ischemia-reperfusion injury. (2013)
  • Author(s): Yoshida T, Kumagai H, Kohsaka T, Ikegaya N.
  • Journal Title: Am J Physiol Renal Physiol Volume: 305
  • Peer Reviewed
• [Journal Article] Development of two murine antibodies against Neospora caninum using phage display technology and application on the detection of N. canimum (2013)
  • Author(s): Jinhua Dong, Takahiro Otsuki, Tatsuya Kato, Tetsuya Kohsaka, Kazunori Ike, and Enoch Y. Park
  • Journal Title: PLoS ONE Volume: 8 Issue: 1 Pages: e53264-e53264
  • DOI: 10.1371/journal.pone.0053264
  • Peer Reviewed
• [Journal Article] Relaxin ameliorates salt-sensitive hypertension and renal fibrosis. (2012)
  • Author(s): Yoshida T, Kumagai H, Suzuki A, Kobayashi N, Ohkawa S, Odamaki M, Kohsaka T, Yamamoto T, Ikegaya N.
  • Journal Title: Nephrol Dial Transplant Volume: 27 Issue: 6 Pages: 2190-2197
  • DOI: 10.1093/ndt/gfr618
  • Peer Reviewed
• [Journal Article] Factors associated with patency of the uterine cervix in bitches with pyometra (2012)
  • Author(s): Tamada H, Kawata N, Kawate N, Inaba T, Kida K, Hatoya S, Akune A, Nakama K, Kohsaka T, Takahashi M, Sawada T
  • Journal Title: Res Vet Sci Volume: 93 Issue: 3 Pages: 1203-1210
  • DOI: 10.1016/j.rvsc.2012.05.012
  • Peer Reviewed
• [Presentation] リラキシン関連因子（ＲＬＦ）の中和化が造精機能に及ぼす影響 (2013)
  • Author(s): 皆川至・佐方醍・柴田昌利・高坂哲也
  • Organizer: 第106回日本繁殖生物学会
  • Place of Presentation: 東京農工大学(東京都府中市）
• [Presentation] 精子核クロマチンの性状解析に基づく新しいウシ精子受精能評価法の確立 (2013)
  • Author(s): 王軍・保田宗行・内山京子・絹川将史・高坂哲也
  • Organizer: 第106回日本繁殖生物学会
  • Place of Presentation: 東京農工大学(東京都府中市）
• [Presentation] LGR8-ectodomainは精巣で発現するリラキシン関連因子受容体LGR8のスプライスバリアントでアンタゴニストとして機能する (2013)
  • Author(s): 植羅直人・高力宙・皆川至・佐々田比呂志・長谷川喜久・高坂哲也
  • Organizer: 第18回日本生殖内分泌学会
  • Place of Presentation: 東京砂防会館・シェーンバッハサボー(東京都千代田区）
• [Presentation] Cisplatin投与で精子形成障害を誘起したラット精巣におけるリラキシンのアポトーシス抑制効果 (2013)
  • Author(s): 森本昌志・吉田卓也・池谷直樹・佐々田比呂志・長谷川喜久・高坂哲也
  • Organizer: 第18回日本生殖内分泌学会
  • Place of Presentation: 東京砂防会館・シェーンバッハサボー(東京都千代田区）
• [Presentation] ブタ精巣におけるリラキシン関連因子（RLF）の発現・分泌動態と生殖細胞に対するパラクリン因子としての機能 (2012)
  • Author(s): 皆川至・佐方醍・柴田昌利・高坂哲也
  • Organizer: 第105回日本繁殖生物学会大会
  • Place of Presentation: 筑波大学大学会館 （茨城県）
• [Presentation] Expression of RLF/INSL3 receptor LGR8 (RXFP2) and function of RLF/INSL3-RXFP2 signaling in germ cells of boar testes (2012)
  • Author(s): Tetsuya Kohsaka, Dai Sagata, Itaru Minagawa, Hiroshi Kohriki, Ali Mohammed Pitia, Yusuke Sugii, Masashi Morimoto, Naoto Uera, Masatoshi Shibata, Hiroshi Sasada, and Yoshihisa Hasegawa
  • Organizer: 6th International Conference on Relaxin and Related peptides
  • Place of Presentation: Chiostro del Maglio, Florence (Italy)
• [Remarks] 静岡大学教員データベース
  • URL: https://tdb.shizuoka.ac.jp/RDB/public/Default2.aspx?id=10880&l=0
• [Remarks] 静岡大学：教員データベース - 高坂 哲也 （KOHSAKA Tetsuya）
  • URL: https://tdb.shizuoka.ac.jp/RDB/public/Default2.aspx?id=10880&l=0