THE STIMULATION OF LIVER ANGIOTENSINOGEN BY GLUCOCORTICOIDS DEPENDS ON THE TYPE OF STEROID AND ITS MODE OF ADMINISTRATION

Glucocorticoids are well known inducers of transcription of the liver angiotensinogen (AOG) gene. However, the doses and the conditions under which they exert this effect in vivo are not known. To investigate this question, we have implanted rats with wax pellets containing 80% corticosterone (B). These pellets increased plasma B and induced clear signs of hypercorticism. However, they did not stimulate plasma AOG, whereas acute injections of dexamethasone (DEX) had a robust effect. In additional experiments, we have determined that: 1) chronic exposure to DEX was less effective than acute DEX in stimulating the production of liver AOG in rats and AOG secretion by rat hepatoma cells; 2) at maximally effective doses, B stimulated the production of AOG by hepatoma cells less effectively than DEX; and 3) DEX had less effect on AOG secretion than on AOG messenger RNA concentration, both in vivo and in vitro. All three mechanisms may have contributed concomitantly to the absence of response of plasma AOG to mild and chronic elevations of plasma B. These results suggest that glucocorticoids are unlikely to be primary regulators of liver AOG.