Opposite regulation of hepatic lipase and lecithin: cholesterol acyltransferase by glucocorticoids in rats.
Rats were treated with hydrocortisone, dexamethasone or triamcinolone for 4 days. The effect of treatment on hepatic lipase and lecithin:cholesterol acyltransferase (LCAT) mRNA levels and catalytic activities was determined. Hepatic lipase mRNA was not affected by hydrocortisone, but was decreased after dexamethasone (-28%) and triamcinolone (-54%). Hepatic lipase activity followed the same pattern, it was not affected by hydrocortisone and lowered by dexamethasone (-38%) and triamcinolone (-70%). The LCAT mRNA level in the liver was also not affected by hydrocortisone, but increased upon treatment with dexamethasone (+22%) and triamcinolone (+72%). Plasma LCAT, determined with an excess exogenous substrate (designated LCAT-II), tended to decrease after hydrocortisone treatment (-11%) and was higher after dexamethasone (+21%) and triamcinolone (+22%). The plasma cholesterol esterification rate (designated LCAT-I), determined by incubation of the plasma at 37 degrees C, followed the same pattern. The activity ratio of hepatic lipase/LCAT-II decreased from 1 in the controls to 0.51 after dexamethasone and 0.25 in the triamcinolone-treated animals. The plasma HDL cholesterol concentration in the different groups changed oppositely to the hepatic lipase/LCAT activity ratio. It is concluded that HDL cholesterol is raised by synthetic glucocorticoids due, among other factors, to a lowered hepatic lipase and an increased plasma LCAT activity. The influence of glucocorticoids on these enzymes is, at least partly, explained by the effects on the hepatic mRNA contents.
Jansen
H
H
Department of Internal Medicine III, Erasmus University, Rotterdam, Netherlands.
van Tol
A
A
Auwerx
J
J
Skretting
G
G
Staels
B
B
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy; D008076:Cholesterol, HDL / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006854:Hydrocortisone / Q000494:pharmacology; D008049:Lipase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014221:Triamcinolone / Q000494:pharmacology
D008076:Cholesterol, HDL; D005938:Glucocorticoids; D012333:RNA, Messenger; D014221:Triamcinolone; D003907:Dexamethasone; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008049:Lipase; D006854:Hydrocortisone