UNSATURATED FATTY-ACIDS SYNERGISTICALLY ENHANCE GLUCOCORTICOID-INDUCED GENE-EXPRESSION

Regulation by unsaturated fatty acids of glucocorticoid-sensitive gene transcription was studied in HeLa cells transiently transfected with a mouse mammary tumour virus-luciferase reporter gene. Arachidonic acid and docosahexaenoic acid by themselves had no effect on basal levels of luciferase expression. However, they were able to enhance dexamethasone-induced transcription by 1.4-2.3 times (25-42 times the central levels) in a dose-dependent manner (ED(50): 18 and 8 mu M) for arachidonic and docosahexaenoic acid, respectively. The glucocorticoid antagonist RU486 effectively antagonized the dexamethasone response as well as the synergistic effect observed in the presence of arachidonic and docosahexaenoic acids, suggesting that the glucocorticoid receptor was an intermediate in the fatty acid synergism of the dexamethasone response. These studies show that fatty acids may be playing a role in modulating the intracellular steroid hormone signalling pathway to co-regulate a glucocorticoid-sensitive promoter.