1998 Fiscal Year Final Research Report Summary
Signal transduction of growth hormone secretion
Project/Area Number |
08457260
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
内分泌・代謝学
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Research Institution | The University of Tokyo |
Principal Investigator |
YAMASHITA Naohide The University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (90174680)
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Co-Investigator(Kenkyū-buntansha) |
YAMASAKI Tomoko The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 教務職員 (60282563)
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Project Period (FY) |
1996 – 1998
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Keywords | Hormone secretion / Growth hormone / Ca2+ channel / cAMP / gsp oncogene / GHRH / folliculo-stellate cells |
Research Abstract |
(1)The relationship between hormone secretion and Ca^<2+>, cAMP : We examined the capacitance-measured hormone secretion (Cm) in human growth hormone (GH)-producing adenoma cells. Cm increased after membrane was depolarized above the threshold for voltage-gated Ca^<2+> channels (VGCC). The increase of Cm was dependent on the magnitude and the duration of membrane depolarization. Application of cAMP analogue, 8Br-cAMP, did not increase Cm below the threshold for VGCC, whereas it caused additional increase of Cm after VGCC was activated, it was concluded that cAMP per se did not increase Cm, and that the influx through VGCC was prerequisite for cAMP-induced hormone secretion. (2)The disturbance of signal transduction by gsp oncogene in human GH-producing adenoma cells : We examined the mutation of Gs alpha mutation (gsp oncogene) in growth hormone releasing hormone (GHRH)-unresponsive tumors. Single cell RT-PCR revealed the presence of gsp mutation in a single cell arid it was heterozygou
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s. This mutation caused constitutive activation of Os protein, which made adenoma cells unresponsive to GHRH.We incorporated gsp mutation in rat GH3, MtT/S cells and mouse AtT/20 cells in order to investigate how gsp mutation related to the pathogenesis of pituitary tumors. (3) K^+ channels and cell contact in pituitary folliculo-stellate cells : Membrane currents in a folliculo-stellate cell line (TtT/GF) were examined. A distinct outward current was observed in isolated spread cells, contact round cells and contact spread cells, whereas the outward current detected in isolated round cells was barely perceivable. The reversal potentials of the outward tail current obeyed the Nernst equation, indicating that the outward current was carried by K^+ ions. The biophysical and pharmacological characteristics of the K^+ current in TtT/GF cells were similar to those of the K^+ current in glial and Schwann cells. According to the results of the present study it was concluded that TtT/GF cells possessed outward K^+ channels, characteristics of which were similar to those of the K^+ channels in glial and Schwann cells, and that the amplitude of the K^+ current in TtT/GF cells appeared to be regulated by the condition of the cell contact. Less
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Research Products
(13 results)
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[Publications] Fujita, H., Matumoto, T., Kawashima, H., Ogata, E., Fujita, T.& Yamashita, N.: "Activation of Cl^- channels by extracellular Ca^<2+> in freshly isolated rabbit osteoclasts." Journal of Cellular Physiology. 169. 217-225 (1996)
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