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2003 Fiscal Year Final Research Report Summary

Mechanism of growth hormone action : Identification of target molecules of GH

Research Project

Project/Area Number 14370328
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKobe University

Principal Investigator

CHIHARA Kazuo  Kobe University, Graduate School of Medicine, professor, 大学院・医学系研究科, 教授 (00107955)

Co-Investigator(Kenkyū-buntansha) IGUCHI Genzou  Kobe University, Hospital, research associate, 医学部附属病院, 助手 (60346260)
TAKAHASHI Yutaka  Kobe University, Graduate School of Medicine, research associate, 大学院・医学系研究科, 助手 (70301281)
OKIMURA Yasuhiko  Kobe University, School of Medicine, associate professor, 医学部, 助教授 (30204100)
Project Period (FY) 2002 – 2003
Keywordsgrowth hormone / signal transduction / anti-aging effect / adipocyte
Research Abstract

To clarify the mechanism of anti-aging effect of growth hormone (GH), mRNA levels in response to hGH were examined with differential display and DNA micro array in GH-targeting cells including vascular smooth muscle cell (VSMC), hepatocytes, and adipocytes. In VSMC, hGH increased cytochrome oxidase subunit II/III mRNA in addition to several unknown mRNAs. The mRNA for mitochondria transcription factor I (mtTFI) that stimulates the expression of cytochrome oxidase subunit II/III was up-regulated by hGH. Pretreatment with JAK2 inhibitor AG490 and a MEK inhibitor PD98059 suppressed mtTFI expression and pretreatment with a PI3 kinase inhibitor wortomannin did not, suggesting that hGH increases mtTFI mRNA levels through JAK2 and MEK signaling in VSMC. This finding afford into the relation of GH and mitochondria. The regulatory mechanism of GH on the mtTFI gene expression is ongoing. In adipocytes, hGH increased several unknown mRNA levels. Some of them increased along with adipocyte differentiation. Expression pattern and homology search suggested some of the GH-induced proteins might play an important role in GH action. Knock out mice of the genes are now being produced to clarify their physiological significance.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yoshioka S: "Up-regulation of mitochondrial transcription factor 1 mRNA levels by GH in VSMC."Life Sci.. 74. 2097-2109 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iida K: "A variety of phenotype with R161Q germline mutation of the von Hippel-Lindau tumor suppressor gene in Japanese kindred."Int J Mol Med.. 13. 401-404 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iida K: "Diverse regulation of full-length and truncated growth hormone receptor expression in 3T3-L1 adipocytes."Mol Cell Endocrinol.. 210. 21-29 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fumoto M: "Cloning of a protein binding to the most proximal Pit-1 binding element of prolactin gene from human pituitary cDNA library."Mol Cell Endocrinol.. 207. 31-38 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakatani T: "Lactogenic hormone responsive element reporter gene activation assay for human growth hormone."Growth Horm IGF Res.. 13. 275-281 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kishimoto M: "The R271W mutant form of Pit-1 does not act as a dominant inhibitor of Pit-1 action to activate the promoters of GH and prolactin genes."Eur J Endocrinol.. 148. 619-625 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kishimoto M: "Cloning and characterization of the 5(')-flanking region of the human ghrelin gene."Biochem Biophys Res Commun.. 305. 186-192 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okimura Y: "The role of circulating ghrelin in growth hormone (GH) secretion in freely moving male rats."Life Sci.. 72. 2517-2524 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaji H: "Adult growth hormone deficiency in Japan : results of investigation by questionnaire."Endocr J.. 49. 597-604 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murata M: "A study of carotid intima-media thickness in GH-deficient Japanese adults during onset among adults and children."Eur J Endocrinol.. 148. 333-338 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kishimoto M: "Novel function of the transactivation domain of a pituitary-specific transcription factor, Pit-1."J Biol Chem.. 277. 45141-45148 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shiro, Yoshioka: "Up-regulation of mitochondrial transcription Factor 1mRNA levels by GH in VSMC."Life Sci.. 74. 2097-2109 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keiji, Iida: "A variety of phenotype with R161Q germline mutation of The von Hippel-Lindau tumor suppressor gene in Japanese Kindred."Int J MolMed. 13. 401-404 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keiji, Iida: "Diverse regulation of full-length and truncated growth Hormone receptor expression in 3T3-L1 adipocytes"Mol Cell Endocrinol. 210. 21-29 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mariko, Fumoto: "Cloning of a protein binding to the most proximal Pit-1 binding element of prolactin gene from human pituitary cDNA Library"Mol and cell Endocrinol. 207. 31-38 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomohisa, Sakatani: "Lactogenic hormone responsive element reporter Gene activation assay for human growth hormone"Growth Horm IGF Res. 13. 275-281 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiko, Kishimoto: "Cloning and characterization of the 5'-flanking Region of the human ghrelin gene"Biochemical and Biophysical Research Communications. 305. 186-192 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiko, Kishimoto: "Mutant from of Pit-1 (R271W) does not act as a Dominant inhibitor of Pit-1 action to activate the promoters of growth Hormone and prolactin genes"Euro J Endocrinol. 148. 619-625 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiro, Murata: "A Study of carotid intima-media thickness in GH-Deficient Japanese adults during onset among adults and children"Euro J Endocrinol. 148. 333-338 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasuhiko, Okimura: "The role of circulating ghrelin in growth hormone (GH) secretion in freely-moving rats"Life Sci. 72. 2517-2524 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hidesuke, Kaji: "Adult growth hormone deficiency in Japan : Results of Investigation by questionnaire"Endocrine J. 49. 597-604 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiko, Kishimoto: "Novel function of transactivation domain of the Pituitary specific transcription factor, Pit-1"J Biol Chem. 277. 45141-45148 (2002)

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

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Published: 2005-04-19  

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