STEROID-HORMONES UP-REGULATE RAT ANGIOTENSIN-II TYPE 1A RECEPTOR GENE - ROLE OF GLUCOCORTICOID-RESPONSIVE ELEMENTS IN RAT ANGIOTENSIN-II TYPE 1A PROMOTER

The transcription of the rat angiotensin II type 1A receptor gene is stimulated by glucocorticoids. To clarify the molecular mechanism for glucocorticoid action in rat vascular smooth muscle cells, we investigated the effects of dexamethasone on the promoter activity of the angiotensin II type 1A receptor by using promoter/luciferase reporter gene constructs and heterologous context constructs (containing the thymidine kinase promoter) in transfected vascular smooth muscle cells. There are three putative glucocorticoid responsive elements in the promoter. However, only one glucocorticoid responsive element was found to respond to dexamethasone (1 mu M). The region was located at positions, similar to 756 to similar to 770 bp upstream of the transcription initiation site. A glucocorticoid antagonist, RU38486, completely blocked the induction by dexamethasone, suggesting that the glucocorticoid responsive element was functional through a specific glucocorticoid receptor. Compared with the angiotension II type 1A receptor promoter, no effect by dexamethasone was observed in vascular smooth muscle cells transfected with the angiotensin II type 1B receptor promoter/luciferase reporter gene constructs. We concluded that the dexamethasone-induced increase in the transcription of the angiotensin II type 1A receptor gene occurred through the binding to GRE up the glucocorticoid-specific receptor.