Inhibitory Effects of Dexamethasone on Epidermal Growth Factor-Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes

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概要

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• We investigated the effects of dexamethasone on epidermal growth factor (EGF)-induced DNA synthesis and proliferation in serum-free primary cultures of adult rat hepatocytes. Isolated hepatocytes were cultured at a density of 3.3×104 cells/cm2 in Williams medium E containing 5% bovine calf serum and various concentrations of dexamethasone for 1, 2 and 3 h. After the 3-h attachment period, the medium was changed, and cells were cultured in serum-free and dexamethasone-free Williams medium E with or without glucocorticoid receptor antagonists. The growth-stimulating effects of EGF (20 ng/ml) on the primary cultured hepatocytes were time- and concentration-dependently inhibited by dexamethasone added to the culture medium. The mineral corticoid aldosterone (10−7 M) did not produce the same growth-inhibitory effects as dexamethasone (10−8 M). The inhibitory effects of dexamethasone were reversed by treatment with the glucocorticoid receptor antagonist mifepristone (RU486, 10−6 M) or a monoclonal antibody against glucocorticoid receptor (100 ng/ml). In addition, the growth-inhibitory effects of dexamethasone did not affect EGF-induced p42 mitogen-activated protein (MAP) kinase phosphorylation. These results indicate that dexamethasone concentration-dependently delays and inhibits the EGF-induced DNA synthesis and proliferation through its own intracellular receptor in primary cultures of adult rat hepatocytes.

• 公益社団法人　日本薬学会の論文

著者

• Ogihara Masahiko

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Josai University

• KIMURA Mitsutoshi

  Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University

• Kimura Mitsutoshi

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Josai University

• Moteki Hajime

  Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Japan

• Moteki Hajime

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Josai University

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• Inhibitory Effects of Dexamethasone on Hepatocyte Growth Factor–Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes
• Inhibitory Effects of Dexamethasone on Epidermal Growth Factor-Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes
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• Inhibitory Effects of Dexamethasone on Hepatocyte Growth Factor-Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes
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