Glucocorticoid receptors in cultured human skin fibroblasts: evidence for down-regulation of receptor by glucocorticoid hormone.

In the present study, we have determined the specific glucocorticoid receptors in cultured human skin fibroblasts with [3H]dexamethasone as the ligand. The whole-cell assay was employed for determination of glucocorticoid receptor densities and binding affinities in fibroblast cultures established either from 16 healthy control subjects, from 4 patients with active progressive systemic sclerosis (PSS), from 3 patients with keloids and 3 patients with diabetes mellitus. The receptor densities in PSS, keloid, diabetes and control fibroblasts were in the same range, the values being 6.3 +/- 4.9, 7.7 +/- 3.6, 5.3 +/- 1.3 and 7.9 +/- 6.2 fmol/micrograms DNA (mean +/- SD), respectively. In further studies, the cells were incubated with 10(-7) M dexamethasone for 4 or 9 days before the receptors were assayed. The specific binding of [3H]dexamethasone in steroid treated cultures was 62 and 13% of that observed in controls, suggesting down-regulation. In contrast, incubation of fibroblasts with 10(-5) M all-trans-retinoic acid did not alter the binding of [3H]dexamethasone, suggesting lack of pharmacologic interference at the receptor level.