Glucocorticoid-stimulated biosynthesis of low density lipoprotein receptor in cultured fibroblasts.
Preincubation of human skin fibroblasts in the presence of 10(-6)-10(-5) mol/l glucocorticoids (dexamethasone) causes a concentration and time-dependent increase of receptor-mediated internalisation of [125I]LDL. This increase is due to a glucocorticoid-specific stimulation by 40-50% of LDL receptor synthesis as demonstrated by an increased incorporation of [35S]methionine into immune precipitated receptor protein. In contrast the rate of synthesis of total cell protein and of lysosomal cathepsin D is not significantly influenced by dexamethasone. The increased LDL receptor synthesis is accompanied by an enhanced synthesis of cholesterol from [2-3H]mevalonolactone and [1-14C]acetate. The glucocorticoid-induced enhancement of LDL receptor and cholesterol synthesis is abolished by preincubation of the cells with dexamethasone in combination with 25-hydroxycholesterol.
Filipovic
I
I
Buddecke
E
E
D000085:Acetates / Q000378:metabolism; D002402:Cathepsin D / Q000096:biosynthesis; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000187:drug effects; D018110:Receptors, Lipoprotein; D012867:Skin / Q000166:cytology; D013997:Time Factors
D000085:Acetates; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C015367:mevalonolactone; D003907:Dexamethasone; D002784:Cholesterol; D008715:Methionine; D002402:Cathepsin D; D008798:Mevalonic Acid