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 control levels) in a dose-dependent manner (ED50: 18 and 8 microM) 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.
INSERM U224, Faculté de Médecine Xavier Bichat, Paris, France.
G
G
Vallette
C
C
Sumida
N
N
Thobie
E A
EA
Nunez
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006367:HeLa Cells / Q000201:enzymology / Q000821:virology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis*; D008324:Mammary Tumor Virus, Mouse / Q000502:physiology; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D005938:Glucocorticoids; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015735:Mifepristone; D003907:Dexamethasone; D008156:Luciferases