Glucocorticoids inhibit the stimulatory effect of epidermal growth factor on the initiation of DNA synthesis.
Confluent, quiescent Swiss 3T3 cells in culture can be stimulated to initiate DNA synthesis and divide by addition of growth factors to the culture medium. Here we show that hydrocortisone and other steroids which have glucocorticoid activity inhibit the stimulation of these cells by epidermal growth factor (EGF) in contrast to their reported enhancement of stimulation by fibroblast growth factor (FGF). Binding studies using [3H]-triamcinolone acetonide show that Swiss 3T3 cells contain a single class of glucocorticoid receptor of uniform affinity (KD = 2.0 nM), and about 34,000 receptor sites per cell. Those steroids which displace bound [3H]-triamcinolone acetonide are also effective in inhibiting the stimulation of DNA synthesis by EGF in the presence or absence of insulin, and the concentration of triamcinolone acetonide required for one-half maximal biological effect is in the same range as the KD. A similar concentration is required for one-half maximal enhancement of the effect of FGF. These results suggest that both the inhibitory and stimulatory effects of glucocorticoids may be mediated via these receptors, the different effects thus being due to differences in the intracellular events triggered by each growth factor.
D000818:Animals; D004261:DNA Replication / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000037:antagonists & inhibitors*; D011965:Receptors, Glucocorticoid; D013268:Stimulation, Chemical; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D005938:Glucocorticoids; D007328:Insulin; D010455:Peptides; D011965:Receptors, Glucocorticoid; D004815:Epidermal Growth Factor; D014222:Triamcinolone Acetonide; D006854:Hydrocortisone