The challenge for a useful therapeutic strategy for infertile male using eNOS-Tg mice

• Project/Area Number: 18390436
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kobe University
• Principal Investigator: FUJISAWA Masato Kobe University, 医学系研究科, 教授 (30243314)
• Co-Investigator(Kenkyū-buntansha): TANAKA Kazushi , 医学部附属病院, 講師 (20335433) ; ISHIKAWA Tomomoto , 医学部附属病院, 医員 (00432576) ; YAMAGUCHI Kouhei 神戸大学, 医学部附属病院, 医員 (50457107) ; GOUDA Kazumasa 神戸大学, 医学(系)研究科, 医学研究員 (80403278)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥12,160,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
• Keywords: 精子形成 / 精細胞 / NO / eNOS / apoptosis

Research Abstract

セルトリ細胞においてIL-1β刺激はJNK経路を介してiNOS発現を亢進させ、NOを生成する。これらの経路の概念は精巣内病態における新たな治療戦略上において重要な一部であり、セルトリ細胞におけるサイトカイン制御機構の解明は精子形成障害の治療に貴重な情報を与えることが期待される。また停留精巣モデルによる精細胞のアポトーシスは血管内皮型一酸化窒素合成酵素強発現マウスにおいて増加したことより、熱ストレスや酸化ストレスに関連する精子形成障害においてeNOSを制御することが有効な治療法になりうる可能性が示唆された。

Research Products

• [Journal Article] Oral Administration of Tetrahydrobiopterin Attenuates Testicular damage by Reducing Nitric Oxide Synthase Activity in a Cryptorchid Mouse Model (2008)
  • Author(s): Kondo Y, Ishikawa T, Yamaguchi K, Yada T, Fujisawa M
  • Journal Title: J Androl 29 Pages: 153-63
  • Peer Reviewed
• [Journal Article] Cisplatin Regulates Sertoli Cell Expression of Transferrin and Interleukins (2008)
  • Author(s): Yamaguchi K, Ishikawa T, Kondo Y, Fujisawa M
  • Journal Title: Mol Cell Endocrinol 283 Pages: 68-75
  • Peer Reviewed
• [Journal Article] The assessment of oxidative stress in infertile patients with varicocele. (2008)
  • Author(s): Sakamoto Y, Ishikawa T, Kondo Y, Yamaguchi K, Fujisawa M
  • Journal Title: BJU Int 101 Pages: 1547-1552
  • Peer Reviewed
• [Journal Article] Oral administration of tetrahydrobiopterin attenuates testicular damage byreducing nitric oxide synthase activity in a cryptorchid mouse model. (2008)
  • Author(s): Kondo Y, Ishikawa T, YamaguchiK, Yada T, Fujisawa M
  • Journal Title: J Androl 29 Pages: 153-163
  • Peer Reviewed
• [Journal Article] Expression and distribution of laminin chains in the testis for patients withazoospermia. (2008)
  • Author(s): Ooba T, Ishikawa T, Yamaguchi K, Kondo Y, Sakamoto Y Fujisawa M
  • Journal Title: J Androl 29 Pages: 147-152
  • Peer Reviewed
• [Journal Article] Cisplatin regulates Sertoli cell expression of transferrin and interleukins. (2008)
  • Author(s): Yamaguchi K, Ishikawa T, Kondo Y, Fujisawa M
  • Journal Title: Mol Cell Endocrinol 283 Pages: 68-75
  • Peer Reviewed
• [Journal Article] Oral Administration of Tetrahydrobiopterin Attenuates Testicular damage by Reducing Nitric Oxide Synthase Activity in a Cryptorchid Mouse Model (2008)
  • Author(s): Kondo Y Ishikawa T, YamaguchiK, Yada T, Fujisawa M
  • Journal Title: J Androl 29 Pages: 153-63
  • Peer Reviewed
• [Journal Article] 研究フロンティアセルトリ細胞においてIL-1βはJNK経路を活性化し、一酸化窒素(NO)発現を亢進させる (2007)
  • Author(s): 石川智基、PATRICIA L. MORRIS、藤澤正人
  • Journal Title: 日本生殖内分泌学会雑 12 Pages: 21-25
  • NAID: 40015686181
  • Peer Reviewed
• [Journal Article] Effect of varicocelectomy on patients with unobstructive azoospermia and severe oligospermia. (2007)
  • Author(s): Ishikawa T, Kondo Y, Ymaguchi K, Sakamoto Y, Fujisawa M.
  • Journal Title: BJU Int. 101(2) Pages: 216-8
  • Peer Reviewed
• [Journal Article] Increased testicular 8-hydroxy-2'-deoxyguanosine in patients with varicocele. (2007)
  • Author(s): Ishikawa T, Fujioka H, Ishimura T, Tkenaka A, Fujisawa M.
  • Journal Title: BJU Int. 100(4) Pages: 863-6
  • Peer Reviewed
• [Journal Article] Assessment of gonadotropin therapy in male hypogonadotropic hypogonadism. (2007)
  • Author(s): Ishikawa T, Ooba T, Kondo Y, Yamaguchi K, Fujisawa M.
  • Journal Title: Fertil Steril. 88(6) Pages: 1697-9
  • Peer Reviewed
• [Journal Article] A Multi-Step Kinase-Based Sertoli Cell Autocrine-Amplifying Loop Regulates Prostaglandins(PG), their Receptors, and Cytokines (2006)
  • Author(s): Ishikawa T, Morris PL
  • Journal Title: Endocrinology 147 Pages: 1706-16
  • Peer Reviewed
• [Journal Article] Interleukin-1β Signals Through a cJun-N-terminal kinase (JNK)-dependent Inducible Nitric Oxide Synthase and Nitric Oxide Production Pathway in Sertoli Epithelial Cells (2006)
  • Author(s): Ishikawa T, Morris PL
  • Journal Title: Endocrinology 147 Pages: 5424-30
  • Peer Reviewed
• [Presentation] 精子形成に関わる精巣内細胞間情報伝達機構 (2008)
  • Author(s): 石川智基
  • Organizer: 第53回日本生殖医学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-23
• [Presentation] セルトリ細胞においてシスプラチンはCOX-2経路を活性化し、プロスタグランディンおよびインターロイキンの産生を誘導する (2007)
  • Author(s): 山口耕平
  • Organizer: 第26回日本アンドロロジー学会
  • Place of Presentation: 浦安
  • Year and Date: 2007-07-05
• [Presentation] セルトリ細胞においてFSH はPKA, PKB, PKC 経路を介しSteroidogenicacute regulatory protein(StAR)を調節する (2007)
  • Author(s): 石川智基
  • Organizer: 第12回日本生殖内分泌学会学術集会
  • Place of Presentation: 東京
• [Presentation] Cisplatin induces interleukin(IL)-1beta and IL-6 expression through a cyclooxygenase 2 regulation of prostaglandin(PG)E2, PGF2alpha, PGD2, and PGI2 production pathway in rat Sertoli cells (2007)
  • Author(s): Yamaguchi K
  • Organizer: American Society for Reproductive Medicine
  • Place of Presentation: 63rd Annual Meeting(Washington D.C)
• [Presentation] セルトリ細胞におけるプロスタグランディンのparacrine/autocrine作用 (2007)
  • Author(s): 石川智基
  • Organizer: 第26回日本アンドロロジー学会
  • Place of Presentation: 浦安
• [Presentation] nterleukin-1β Signals Through a cJun-N-terminal kinase (JNK)-dependent Inducible Nitric Oxide Synthase and Nitric Oxide Production Pathway in Sertoli Epithelial Cells (2007)
  • Author(s): Ishikawa T
  • Place of Presentation: AUA annual meeting、Anaheim
• [Presentation] セルトリ細胞におけるproinflammatory cytokine のautocrine loop (2006)
  • Author(s): 石川智基
  • Organizer: 第21回日本生殖免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2006-12-02
• [Presentation] セルトリ細胞においてIL-1βはJNK経路を活性化し、一酸化窒素(NO)発現を亢進させる (2006)
  • Author(s): 石川智基
  • Organizer: 第11回日本生殖内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2006-11-25
• [Presentation] セルトリ細胞におけるIL-1βのparacrine/autocrine機構 (2006)
  • Author(s): 石川智基
  • Organizer: 第32回関西アンドロロジーカンファレンス
  • Place of Presentation: 大阪
  • Year and Date: 2006-03-04
• [Presentation] セルトリ細胞においてインターロイキン1βはJNK, COX-2経路を介しサイトカインを誘導する (2006)
  • Author(s): 石川智基
  • Organizer: 第15回泌尿器科分子・細胞研究会
  • Place of Presentation: 京都
  • Year and Date: 2006-02-25
• [Presentation] Multiple protein kinases mediate follicle stimulating hormone (FSH) regulation of steroidogenic acute regulatory(STAR)-related lipid transfer proteins in Sertoli cell (2006)
  • Author(s): Ishikawa T
  • Organizer: 2^<nd> Asia Pacific Forum on
  • Place of Presentation: Andrology meeting、Shanghai
• [Presentation] セルトリ細胞におけるproinflammatory cytokine のparacrine/autocrine 機構 (2006)
  • Author(s): 石川智基
  • Organizer: 第26回日本アンドロロジー学会
  • Place of Presentation: 金沢
• [Presentation] Multiple protein kinases mediate follicle stimulationg hormone (FSH) regulation of Sertoli cell steroidogenic acute regulatory (StAR)-related lipid transfer (START-domain-containing) proteins (2006)
  • Author(s): Ishikawa T
  • Place of Presentation: ASA annual meeting、Chicago
• [Presentation] 精子形成障害 : 間質細胞からのアプローチ (2006)
  • Author(s): 石川智基
  • Organizer: 第94回日本泌尿器科学会
  • Place of Presentation: 福岡
• [Presentation] A multi-step kinase-based Sertoli cell autocrine-amplyfying loop regulates prostaglandins
  • Author(s): Ishikawa T
  • Organizer: their receptors, and cytokines,AUA annual meeting
  • Place of Presentation: Atlanta
• [Presentation] Follicle stimulationg hormone(FSH)regulates Sertoli cell expression of steroidogenic acute regulatory-related lipid transfer(START-domain)proteins by activation of protein kinase A(PKA) and C(PKC)
  • Author(s): Ishikawa T
  • Organizer: AUA annual meeting
  • Place of Presentation: Atlanta