Stimulation of bovine pulmonary artery endothelial cell ACE by dexamethasone: involvement of steroid receptors.
After exposure of bovine pulmonary artery endothelial cells in culture to 1 microM dexamethasone for 24-48 h, angiotensin-converting enzyme (ACE) activity of these cells was elevated severalfold. The increase in ACE activity was preceded by an increase in ACE mRNA, which could be detected after treatment of cells with dexamethasone for 4 h. When the increase in ACE mRNA produced by dexamethasone at 4 h was blocked by alpha-amanitin, an RNA polymerase II inhibitor, the increase in ACE activity detected at 48 h was inhibited. RU 38486, a steroid receptor antagonist, inhibited the elevation of both ACE activity and mRNA produced by dexamethasone. Among other steroids tested, only hydrocortisone, aldosterone and corticosterone-21-acetate had a stimulatory effect on ACE activity. RU 38486 effectively blocked the elevation in ACE activity produced by both aldosterone and dexamethasone, but had no effect on the elevation of ACE activity produced by other agents (3-isobutyl-1-methylxanthine, A23187, and dibutyryl adenosine 3',5' cyclic monophosphate). From these data we conclude that dexamethasone and certain other steroids with an hydroxyl group in the 11th carbon position regulate ACE gene expression of bovine endothelial cells at the transcriptional level via a steroid receptor-mediated mechanism.
Dasarathy
Y
Y
New England Medical Center, Boston, Massachusetts 02111.
Lanzillo
J J
JJ
Fanburg
B L
BL
D000450:Aldosterone / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D015735:Mifepristone / Q000494:pharmacology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D011987:Receptors, Steroid / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D015335:Molecular Probes; D012333:RNA, Messenger; D011987:Receptors, Steroid; D015735:Mifepristone; D000450:Aldosterone; D003907:Dexamethasone; D003513:Cycloheximide; D007703:Peptidyl-Dipeptidase A