title: Inhibitory effects of dexamethasone on epidermal growth factor-induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan. mkimura@josai.ac.jp
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Kimura
authors.forename: Hajime
authors.initials: H
authors.lastname: Moteki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ogihara
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003470:Culture Media; D004261:DNA Replication / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003470:Culture Media; D015735:Mifepristone; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases