REGULATION BY GLUCOCORTICOIDS OF ANGIOTENSINOGEN GENE-EXPRESSION AND SECRETION IN ADIPOSE-CELLS

Adipose cells are an important source of angiotensinogen (AT). Its act ivation product, angiotensin II, stimulates in vitro and in vivo the p roduction and release of prostacyclin which acts as a potent adipogeni c signal in promoting the terminal differentiation of preadipocytes to adipocytes. Since glucocorticoids are known to promote adipose cell d ifferentiation in vitro as well as in vivo, their role in the regulati on of AT gene expression and secretion has been investigated in cultur ed Ob1771 mouse adipose cells. In contrast with liver cells, which are the major source of AT and the target of several hormones for the reg ulation of its expression, adipose cells are only responsive to glucoc orticoids, which are able to up-regulate AT gene expression and AT sec retion rapidly and dose-dependently. On exposure to glucocorticoids, a ccumulation of AT mRNA appears primarily to be due to transcriptional activation of the gene and is parallelled by secretion of the protein. Similar results on AT mRNA expression and AT secretion were obtained using explants of rat adipose tissue ex vivo demonstrating a major if not exclusive mechanism of regulation, of AT production by glucocortic oids in mature adipose cells. Together these results provide a potenti al link between glucocorticoids, AT, the growth of adipose tissue and increased blood pressure.