In vitro studies of skin fibroblasts from a patient with a new type of primary cortisol resistance: glucocorticoid receptor status and glucocorticoid effect on DNA synthesis.
Studies made on cultured skin fibroblasts obtained from a patient with primary cortisol resistance are described. Whole cell in vitro assays, using the patient's fibroblasts revealed a reduction in the dexamethasone binding capacity (7.86 +/- 0.73 fmol/micrograms DNA, mean +/- SD, n = 3; normal: 15.2 +/- 1.90 fmol/micrograms DNA, n = 8) and an apparently normal dissociation constant (3.69 +/- 0.15 nM; normal: 3.74 +/- 0.40 nM). In addition, the effects of glucocorticoids on DNA synthesis in these cells were examined. DNA synthesis was inhibited by dexamethasone both in normal fibroblasts and in the patient's cells, but the patient's cells were less sensitive to this inhibition, indicating resistance of the cells to glucocorticoid in vitro. These results suggest that the resistance of target tissues to glucocorticoids is due to the reduction in receptor number and that this is the primary defect in this new type of primary cortisol resistance in man.
D000328:Adult; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D004247:DNA; D006854:Hydrocortisone