Glucocorticoids enhance somatomedin-C binding and stimulation of amino acid uptake in human fibroblasts.

Abstract

The regulation of growth by the GH-dependent mitogen somatomedin-C (Sm-C) may involve not only changes in circulating levels of Sm-C, but also alterations in cellular sensitivity to Sm-C induced by humoral factors. Glucocorticoids have been reported to enhance the stimulatory effect of Sm-C on DNA synthesis and cell replication in cultured human fibroblasts, but the cellular alteration responsible for this effect was not fully defined. Using an assay for cellular sensitivity to Sm-C based on stimulation of uptake of the amino acid analog aminoisobutyric acid, a 20-h preincubation with 100 nM dexamethasone was found to enhance both the sensitivity and the maximal responsiveness of human fibroblasts to a 3-h incubation with Sm-C. This effect was found using fibroblasts from multiple normal donors of different ages, and dexamethasone was approximately 10-fold more potent than hydrocortisone. The glucocorticoid antagonist RU486 (100 nM) largely reversed the enhancing effect of 100 nM dexamethasone on Sm-C action. Binding of [125I]Sm-C to intact fibroblast monolayers or trypsin-dispersed cells could be increased by 60-80% by glucocorticoid preincubation, and this increase correlated well with enhanced stimulation of [3H]aminoisobutyric acid uptake, suggesting that the enhancement of Sm-C action in glucocorticoid-treated cells may be mediated at the level of the Sm-C receptor.