title: Effects of brief glucocorticoid exposure on growth of vascular smooth muscle cells in culture.
abstract: While prolonged exposure of vascular smooth muscle cells (VSMC) to glucocorticoid has been shown to inhibit cell proliferation, the effect of a brief pulse exposure is not known. We studied the short-term effects of pulse exposure to dexamethasone (DEX) on DNA synthesis in cultured VSMC. VSMC were pulsed with DEx for varying time intervals and [3H]thymidine incorporation into cells after 24 h was measured. Exposure to DEX for 24 h decreased [3H]thymidine incorporation, while pulse treatments with DEX from 2 min to 6 h significantly increased [3H]thymidine incorporation. Maximal proliferative effect was observed with a 20-min exposure. The effect of a 20-min pulse was dose-dependent, with the half-maximal dose of DEX being approximately 10(-7) M. A selective glucocorticoid receptor antagonist, RU486, inhibited the proliferative effect of DEx. Concentrated conditioned medium from cells exposed to 10(-6) M DEX increased [3H]thymidine incorporation by other VSMC in a dose-dependent manner. These results suggest that short-term pulse DEX exposure is capable of producing one or more autocrine growth factors in VSMC via a glucocorticoid receptor action. This effect of glucocorticoid pulses may contribute to the pathogenesis of arteriosclerosis and hypertension.
authors.affiliation: Third Department of Internal Medicine, Fukui Medical University, Matsuokacho, Japan. Kawai@fmsrsa.fukui-med.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kawai
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
authors.forename: K
authors.initials: K
authors.lastname: Asazuma
authors.forename: K
authors.initials: K
authors.lastname: Masamura
authors.forename: A
authors.initials: A
authors.lastname: Iwamuro
authors.forename: Y
authors.initials: Y
authors.lastname: Takano
authors.forename: H
authors.initials: H
authors.lastname: Tada
authors.forename: S
authors.initials: S
authors.lastname: Matsukawa
authors.forename: I
authors.initials: I
authors.lastname: Miyamori
mesh_terms: D000818:Animals; D001011:Aorta; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D013936:Thymidine / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone; D003907:Dexamethasone; D013936:Thymidine