Glucocorticoids inhibit the stimulatory effect of epidermal growth factor on the initiation of DNA synthesis

Abstract

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.

Mitogenic effect of double‐stranded RNA in human fibroblasts: Role of autogenous interferon

“…Inhibitory effects of glucocorticoids on cell proliferation have also been reported (Cristofalo and Rosner, 1981;Otto et al, 1981;Chen et al, 1983). We examined the effect of dexamethasone on the mitogenic action of poly(I).poly(C) in FS-4 cultures.…”

The uncoupling of macromolecular synthesis from cell division in SV3T3 cells by glucocorticoids: The imposition of a G2 block

“…This is typified by the untransformed mouse fibroblast 3T3 cell line in which it has been shown (Holley and Kiernan, 1974;Otto et al, 1981) that dexamethasone synergizes with fibroblast growth factor (FGF) and insulin to facilitate the transition from G1 to s. In fact, there steroids can provoke a new round of cell division in confluent, density-inhibited 3T3 cells (Thrash and Cunningham, 1973).…”

Glucocorticoid receptor-dependent inhibition of cellular proliferation in dexamethasone-resistant and hypersensitive rat hepatoma cell variants.

“…Growth-inhibiting factors include a wide range of extracellular hormone and hormone-like signalling molecules such as steroids, transforming growth factor type beta, tumor necrosis factor, lymphotoxin, and interferons as well as intracellular activities assigned to putative tumor-suppressing genes (12,33). Evidence also suggests that some growth inhibitors exert their effects by blocking the action of stimulatory growth factors or their receptors (5,40,50). Many specific growth-inhibitory substances have been identified, but their modes of action have not been clearly delineated.…”