Antagonist effect of RU 486 on transcription of glucocorticoid-regulated genes.
The effect of RU 486, a synthetic steroid that is a powerful antagonist of glucocorticoid hormones, was tested on the transcription of several glucocorticoid-regulated genes in different cell types: inflammatory murine macrophages and two human mammary gland-derived cell lines, MDA-MB-231 and HBL-100. The transcription of genes which are positively regulated by glucocorticoids (e.g., tissue-type plasminogen activator and c-myc in mammary cells, c-fos in macrophages) and that of genes which are negatively regulated by these agents (e.g., urokinase-type plasminogen activator in all three cell types, TNF-a and IL-1 in macrophages) was explored. RU 486 almost completely prevented the effects of dexamethasone on the transcription of these various genes. When added alone, RU 486 had essentially no agonist activity.
D000818:Animals; D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D015735:Mifepristone; D010960:Plasminogen Activators / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
D004963:Estrenes; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone; D003907:Dexamethasone; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator