Effects of brief glucocorticoid exposure on growth of vascular smooth muscle cells in culture.
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.
Kawai
Y
Y
Third Department of Internal Medicine, Fukui Medical University, Matsuokacho, Japan. Kawai@fmsrsa.fukui-med.ac.jp
Hayashi
T
T
Eguchi
K
K
Asazuma
K
K
Masamura
K
K
Iwamuro
A
A
Takano
Y
Y
Tada
H
H
Matsukawa
S
S
Miyamori
I
I
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
D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone; D003907:Dexamethasone; D013936:Thymidine