Regulation of angiotensinogen mRNA accumulation in rat hepatocytes.
Experiments were undertaken using isolated rat liver cells to determine whether the stimulation of angiotensinogen synthesis by glucocorticoids, estrogens, and angiotensin II is due to a direct action on the liver and whether these effects involve an increase in angiotensinogen mRNA levels. Dexamethasone and other corticosteroids stimulated angiotensinogen mRNA accumulation in hepatocytes up to 3.5-fold after 2.5-3 h of incubation. The effect of dexamethasone was inhibited competitively by the glucocorticoid antagonist RU486. These results indicate that the stimulation of hepatic angiotensinogen production by glucocorticoids is a direct, receptor-mediated effect and occurs via an increase in angiotensinogen mRNA accumulation. The stimulatory diastereomer of adenosine 3',5'-cyclic phosphorothioate, an active adenosine 3',5'-cyclic monophosphate analogue, caused a 1.8-fold increase in angiotensinogen mRNA accumulation, and this effect was additive with that of dexamethasone, suggesting a distinct mechanism of action. Angiotensin II increased angiotensinogen mRNA levels by only 1.2-fold after 2.5 h, whereas ethinyl estradiol had no effect.
Ben-Ari
E T
ET
Department of Pharmacology, University of Virginia, Charlottesville 22908.
Garrison
J C
JC
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D015735:Mifepristone; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D004963:Estrenes; D004967:Estrogens; D012333:RNA, Messenger; D013873:Thionucleotides; D000808:Angiotensinogen; C016957:adenosine-3',5'-cyclic phosphorothioate; D015735:Mifepristone; D003907:Dexamethasone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate