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ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE FAMILY IN RAT PITUITARY GH3 CELLS

Research Project

Project/Area Number 10671541
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIYAZAKI Kohji  Shimane Medical University, Obstetrics & Gynecology, Professor, 医学部, 教授 (50145322)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsProlactin / Growth hormone / TRH / MAP kinase / myosin light chain kinase / CaM kinase II / apoptosis / bromocriptine / 42 MAPキナーゼ / 細胞内情報伝達系 / MAPキナーゼ / 成長ホルモン
Research Abstract

In GH3 cells, we examined the Mitogen-activated protein kinase (MAP kinase) activation induced by thyrotropin-releasing hormone (TRH) and the role of MAP kinase activation in secretory processes and prolactin (PRL) synthesis. Immunoblotting analysis indicated the presence of only 42 kDa MAP kinase in GH3 cells. TRH induced rapid activation of MAP kinase, which reached a maximal peak of 300 A ィイD4oィエD4i at 5-10 min. TRH-induced MAP kinase activation was inhibited completely by PD098059, and 80 % by calphostin C, respectively. Genistein and removal of extracellular Ca2+ also partially inhibited TRH-induced MAP kinase activation. These results suggest that TRH-induced MAP kinase activation is largely PKC-dependent and partially dependent on the Ca2+-dependent tyrosine kinase. CTPcAMP increased MAP kinase activity significantly, and CPTcAMP effects were inhibited by PD098059. TRH-induced prolactin secretion was not affected by exposure to PD098059, but completely blocked by either wortmannin or KN93. Synthesis of PRL induced by TFH was completely blocked by addition PC098059. These results suggest that TRH-induced MAP kinase activation is correlated with synthesis of PRL but not with PRL secretion. TRH increased the PRL synthesis, while growth hormone synthesis largely decreased by TRH. Treatment of GH3 cells with bromocriptine for 48th increased the p38 MAP kinase activity, and simultaneously increased the number of apoptotic cells. SB202190 and SB203580 completely inhibited the bromocriptine-induced p38 MAP kinase activation, and reduced the number of apoptotic cells. We have shown that TRH induces P44/42 MAP kinase activation in GH3 cells. TRH may be involved in PRL secretion through activation of myosin light chain kinase and CaM kinase II, and in PRL synthesis and differentiation of the cells through activation of P44/42 MAP kinase. The p38 MAP kinase activation induced by bromocriptine was strongly involved in induction of apoptosis.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Haruhiko Kanaski et al.: "Mitogen-Activated Protein Kinase Activation by Stimulation with Thyrotropin-releasing Hormone in Rat Pituitary GH3 cells"BIOLOGY OF REPRODUCTION. 61. 319-325 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruhiko Kanaski et al.: "Involvement of p38 Mitogen-activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 cells"BIOLOGY OF REPRODUCTION. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruhiko Kanasaki: "Mitogen-Activated Protein Kinase Activation by Stimulation with Thyrotropin-Releasing Hormone in Rat Pituitary CH3 Cells"Biology of Reproduction. Vol. 61, No. 1. 319-325 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruhiko Kanasaki: "Involvement of p38 Mitogen-activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 Cells"Biology of Reproduction. (In press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruhiko Kanasaki et al.: "Mitogen-Avtivated Protein Kinase Activation by Stimulation with Thyrotropin-Releasing Hormone in Rat Pituitary GH3 cells"BIOLOGY OF REPRODUCTION. 61. 319-325 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haruhiko Kanasaki et al.: "Involvemet of p38 Mitogen-Activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 cells"BIOLOGY OF REPRODUCTION. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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