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1998 Fiscal Year Final Research Report Summary

Molecular biologic analysis of gonadotropin genes in patients with ovulation disorders caused by pituitary dysfunction

Research Project

Project/Area Number 08457440
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNagoya University

Principal Investigator

SUGANUMA Nobuhiko  Nagoya University, School of Medicine, Associate Professor, 医学部, 助教授 (30179113)

Project Period (FY) 1996 – 1998
Keywordsovulation disorders by pituitary dysfunction / gonadotropin / gonadotropin-releasing hormone / gene mutation
Research Abstract

Female reproductive function is regulated by hypothalamic-pituitary-ovarian system. Pulsatile released gonadotropin-releasing hormone (GnRH) from hypothalamus stimulates the secretion of pituitary gonadotropins (FSH and LH) that not only induce ovarian follicle growth and ovulation but also produce ovarian steroid hormones (estrogen and progesterone) . The syntheses of these hormones are regulated each other through the feed-back mechanism. Abnormalities in this system causes ovulation disorders. In the patients with pituitary dysfunction, abnormalities in the following parts are speculated : 1) Response to GnRH (GnRH receptor), 2) Signal transduction after binding of GnRH to GnRH receptor, 3) Regulatory elements for gonadotropin gene expression, and 4) Gonadotropin genes. Thus, we tried to detect the causes of ovulation disorders by pituitary dysfunction in the present research project.
Six female patients with ovulation disorders by pituitary dysfunction were prepared at Nagoya University Hospital. Lymphocytes were collected from the patients, and DNAs were extracted by guanidium method. Genes of GnRH receptor, LHbeta-subunit, and 300-bp upstream of gonadotropin alpha-subunit were amplified by PCR technic using these DNA as templates. The amplified DNA was cloned to plasmid through TA cloning and sequenced. As results, no abnormalities were found in the above genes in all the patients.
Additionally, new findings in anomalous LH and relationship between structure and function of gonadotropin subnits were gotten. Moreover, gonadotropin effects to some gene expression in oocyte and granulosa cells and clinical significance of GnRH agonist were also studied.

  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Nobuhiko Suganuma: "Effects of the mutations (Trp^8→drg.and Ile^<15>→Thr) in human luceimzing hormone (2H)β-subunit an LH bioactivity in vitro and in vivo" Endocrinology. 137. 831-838 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Madoka Furuhashi: "Disulfide bonds 7-31 and 59-87 of the α-subunit play a different role in assembly of human chorionic gonadotropin and Intropin" Endocrinology. 137. 4196-4200 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shintaro Tate: "Direct effects of estradiol and tumoxifen on gene expressions of inhibin α- and βA-subunits in rat granulosa cells in vitro." Endcrine J.43. 621-628 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼信彦: "LH構造異常症" 産婦人科治療. 72. 91-96 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Ben-Menahem: "The biological action of single chain choriogonaclotropin is exiancoupled from the native hetertdimeric interaction between the α and β subunits" J.Biol.Chem.272. 6827-6830 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayuki Moriwaki: "Alteration of x-linked oligosaccharide structures of human chorionlc gonadotropin β-subunit by disruption of disulfide bonds" Glycoconjugate J.14. 225-229 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuo Hanai: "Effects of gonadotiopin,estrogen and progesterone on c-mos gene expression in mouse cocytes in vivo and in vitro" J.Obstet.Gynaecol.Res.23. 389-397 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼信彦: "LH構造異常症" 産婦人科の世界. 49. 513-520 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼信彦: "黄体化ホルモン・β-サブユニットの突然変異と月経異常" 産科と婦人科. 64. 1355-1360 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shoji Suzuki: "Induction of immediat early genes (IEGS) and rot-1 by human chorionic gonadotropin in murinc Leyding cell line (11A-10)" Biochem.Mol.Bio.Inc.44. 217-224 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼信彦: "黄体化ホルモンβ-サブユニットの異常" 小児内科. 30. 1065-1067 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼信彦: "GnRHアゴニストによる治療-適応基準と問題点:卵巣過排卵刺激法(COH)" 臨床婦人科産科. 53. 180-182 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼 信彦: "Annual Review 内分泌・代謝1997(分担:LH構造異常症)" 中外出版社(岡博、金澤康徳、武谷雄二、田中孝司、編), 282(50-53) (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼 信彦: "新女性医学大系12、排卵と月経(分担、間脳-下垂体系:ゴナドトロピンの構造と作用" 中山書店(武谷雄二、青野敏博、麻生武志、中野仁雄、野澤志朗、 岡村均、編), 401(83〜97) (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅沼 信彦: "図説産婦人科VIEW-31/生殖内分泌・不妊・不妊の基礎(分担:ゴナドトロピンの構造とその異常)" メジカルビュー社, 193(52〜61) (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suganuma N,et al.: "Effects of the mutations (Trp^8-Arg and Ile^<15>-Thr) in human luteinizing hormone (LH) beta-subunit on LH bioactivity in vitro and in vivo." Endocrinology. 137. 831-838 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furuhashi M,et al.: "Disulfide bonds 7-31 and 59-87 of the alpha-subunit play a different role in assembly of human chorionic gonadotropin and lutropin." Endocrinology. 137. 4196-4200 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tate S,et al.: "Direct effects of estradiol and tamoxifen on gene expressions of inhibin alpha- and betaA- subunits in rat granulosa cells in vitro." Endocrine J. 43. 621-628 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ben-Menahem D,et al.: "The biologic action of single chain choriogonadotropin is uncoupled from the native heterodimeric interaction between the alpha and beta subunits." J Biol Chem. 272. 6827-6830 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Moriwaki T,et al.: "Alteration of N-linked oligosaccharide structures of human chorionic gonadotropin beta-subunit" Glycoconjugate J. 14. 225-229 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanai K,et al.: "Effects of gonadotropin, estrogen and progesterone on c-mos gene expression in mouse oocytes in vivo and in vitro." J Obstet Gynaecol Res. 23. 389-397 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki S,et al.: "Induction of immediate early genes (IEGS) and ref-1 by human chorionic gonadotropin in murine Leydig cell line (MA-10)." Biochem Mol Bio Int. 44. 217-224 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N.: "Anomalous structure of LH.(Japanese)" Obst Gynec Therapy. 72. 91-96 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N.: "Anomalous structure of LH.(Japanese)" World Obst Gynec. 49. 513-520 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N.: "Mutations in LH beta-subunit and menstrual disorders.(Japanese)" Obst Gynec. 64. 1355-1360 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N.: "Abnormality in LH beta-subunit.(Japanese)" Pediatric Int Med. 30. 1065-1067 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N,et al.: "Therapy of GnRH agonist : Controlled ovarian hyperstimulation (COH).(Japanese)" Clin Gynec Obst. 53. 180-182 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N.: "Anomalous structure of LH.(Japanese)" Annual Rev Endo Metab. 1997. 50-53 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N.et al.: "Structure and function of gonadotropins.(Japanese)" Shin Joseiigaku Taikei. 12. 83-97 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suganuma N.et al.: "Structure of gonadotropins and their abnormalities.(Japanese)" Zusetsu Obst Gynec View. 31. 52-61 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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