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 fa tty acids modulate glucocorticoid receptor binding, we investigated th e in vitro effect of fatty acids on [H-3]triamcinolone acetonide (TA) binding to the cytosolic glucocorticoid receptor in L2 cells, a cell l ine cloned from the adult rat type II cell. The L2 cell glucocorticoid receptor exhibited specific binding of [H-3]TA which was saturable an d appeared to be a single species of binding sites with an apparent K( D) = 4.9 +/- 3.7 nM and B(max) = 395.4 +/- 84.4 fmol/ mg protein. The receptor had the ligand specificity typical of a physiologically relev ant glucocorticoid receptor. Long-chain unsaturated fatty acids (oleic acid [18:1], linoleic acid [18:2], and arachidonic acid [20:4]) marke dly inhibited [H-3] TA specific binding in a dose-dependent manner, bu t long-chain saturated fatty acids (myristic, 14:0; palmitic, 16:0; an d stearic acid, 18:0) and phospholipids had no effect. Scatchard analy sis revealed a noncompetitive type of inhibition by unsaturated fatty acids. This suggests that unsaturated fatty acids modulate L2 cell glu cocorticoid receptor by binding to sites different from the glucocorti coid binding sites in the receptor. We propose that unsaturated fatty acids may act as negative feedback modulators of glucocorticoid-recept or binding in the lung.