Regulation of liver angiotensinogen mRNA by glucocorticoids and thyroxine.
This study examines the immediate and longer-term changes in angiotensinogen mRNA and in plasma angiotensinogen which follow the withdrawal and replacement of glucocorticoids or thyroxine. RNA from rat liver was analysed by Northern blot and dot-blot hybridization with a 40-mer oligodeoxynucleotide probe specific for angiotensinogen mRNA. Adrenalectomy decreased plasma angiotensinogen and angiotensinogen mRNA to 55 and 50% of control values respectively over a period of 16 days. Similar decreases were obtained after propylthiouracil (1 mg/kg for 16 days) treatment, except when injected simultaneously with T3 (3 micrograms/kg/day). Over the same period plasma renin activity increased in adrenalectomized rats from 4.1 +/- 0.8 to 7.0 +/- 1.5 pmol angiotensin I (AI)/ml/h, and decreased in propylthiouracil-treated rats from 3.8 +/- 0.4 to 1.6 +/- 0.4 pmol AI/ml/h. Approximate half-times of 2-3 days were calculated for both plasma angiotensinogen and angiotensinogen mRNA post-adrenalectomy or after propylthiouracil treatment. Dexamethasone (400 micrograms/kg, i.m.) given to intact rats rapidly increased angiotensinogen mRNA to a maximum of 250% of control by 8 h and with a half-maximal response of 2.8 h. Plasma angiotensinogen responded similarly, apart from an initial delay of 2 h. Treatment with different doses of propylthiouracil and dexamethasone showed that responses were dose-related. We conclude that changes in plasma angiotensinogen and angiotensinogen mRNA are closely correlated, and that under various physiological circumstances angiotensinogen mRNA has a rapid rate of accumulation but a slow rate of decay.
Sernia
C
C
Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Australia.
Clements
J A
JA
Funder
J W
JW
D000315:Adrenalectomy; D000808:Angiotensinogen / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D011441:Propylthiouracil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000494:pharmacology
D012333:RNA, Messenger; D014284:Triiodothyronine; D000808:Angiotensinogen; D011441:Propylthiouracil; D003907:Dexamethasone; D013974:Thyroxine