Unsaturated fatty acid modulation of glucocorticoid receptor binding in L2 cells.
Glucocorticoids stimulate fatty acid synthesis during late fetal lung development by inducing fatty acid synthetase. To determine whether fatty acids modulate glucocorticoid receptor binding, we investigated the in vitro effect of fatty acids on [3H]triamcinolone acetonide (TA) binding to the cytosolic glucocorticoid receptor in L2 cells, a cell line cloned from the adult rat type II cell. The L2 cell glucocorticoid receptor exhibited specific binding of [3H]TA which was saturable and appeared to be a single species of binding sites with an apparent KD = 4.9 +/- 3.7 nM and Bmax = 395.4 +/- 84.4 fmol/mg protein. The receptor had the ligand specificity typical of a physiologically relevant glucocorticoid receptor. Long-chain unsaturated fatty acids (oleic acid [18:1], linoleic acid [18:2], and arachidonic acid [20:4]) markedly inhibited [3H]TA specific binding in a dose-dependent manner, but long-chain saturated fatty acids (myristic, 14:0; palmitic, 16:0; and stearic acid, 18:0) and phospholipids had no effect. Scatchard analysis revealed a noncompetitive type of inhibition by unsaturated fatty acids. This suggests that unsaturated fatty acids modulate L2 cell glucocorticoid receptor by binding to sites different from the glucocorticoid binding sites in the receptor. We propose that unsaturated fatty acids may act as negative feedback modulators of glucocorticoid-receptor binding in the lung.
Viscardi
R M
RM
Department of Pediatrics, University of Maryland School of Medicine, Baltimore.
Max
S R
SR
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001667:Binding, Competitive; D002460:Cell Line; D003902:Detergents; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000378:metabolism; D014316:Tritium
D003902:Detergents; D005231:Fatty Acids, Unsaturated; D005938:Glucocorticoids; D008041:Linoleic Acids; D009829:Oleic Acids; D011965:Receptors, Glucocorticoid; D014316:Tritium; D016718:Arachidonic Acid; D019301:Oleic Acid; D019787:Linoleic Acid; D014222:Triamcinolone Acetonide