Inhibitory Effects of Dexamethasone on Epidermal Growth Factor-Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes
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- Kimura Mitsutoshi
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University
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- Moteki Hajime
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University
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- Ogihara Masahiko
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University
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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.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 34 (5), 682-687, 2011
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204625190144
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- NII論文ID
- 130000657780
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 11057905
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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