Abstract
Glucocorticoids act synergistically with insulin‐like growth factor I (IGF‐I) to stimulate DNA synthesis and replication of cultured human fibroblasts. In the present study, we further define glucocorticoid and IGF‐I interactive effects on human fibroblast metabolism and growth. IGF‐I stimulated dose‐dependent increases in early metabolic events. Half‐maximal effectiveness was seen at 5–8 ng/ml IGF‐I, with mean maximal responses of 1.5‐, 2‐, and 6‐fold for [^3^H]2‐deoxyglucose uptake, [^14^C]glucose incorporation, and [^14^C]aminoisobutyric acid (AIB) uptake, respectively. A 48‐hour preincubation with 10^−7^ M dexamethasone markedly enhanced both the sensitivity and maximal effectiveness of IGF‐I stimulation of AIB uptake. In contrast, dexamethasone had no effect on IGF‐I‐stimulated glucose uptake and utilization. Maximum specific binding of [__125__I]IGF‐I to fibroblast monolayers was identical in ethanol control and glucocorticoid‐treated cells, with 50% displacement at ∼5 ng/ml IGF‐I. In addition to its synergism with IGF‐I, preincubation with dexamethasone augmented insulin and epidermal growth factor (EGF) stimulation of [^3^H]thymidine incorporation; dexamethasone had no effect on platelet‐derived growth factor or fibroblast growth factor action. Two‐dimensional gel electrophoresis identified two specific glucocorticoid‐induced proteins in human fibroblast cell extracts with molecular weights of 45K and 53K and pls of 6.8 and 6.3, respectively. These data indicate that IGF‐I receptor‐mediated actions in human fibroblasts are differentially modulated by glucocorticoids. Glucocorticoids are synergistic with IGF‐I in stimulating mitogenesis and amino acid uptake, without having any apparent effect on IGF‐I‐stimulated glucose metabolism. Glucocorticoid enhancement of growth factor bioactivity may involve modulation of a regulatory event in the mitogenic signaling pathway subsequent to cell surface receptor activation. © 1995 Wiley‐Liss, Inc.