title: Regulation of angiotensinogen mRNA accumulation in rat hepatocytes.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville 22908.
authors.forename: E T
authors.initials: ET
authors.lastname: Ben-Ari
authors.forename: J C
authors.initials: JC
authors.lastname: Garrison
mesh_terms: 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
chemical_list: 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