Reduced sensitivity of peripheral cells to glucocorticoids in hypercholesterolemia.
It has been found that lymphocytes of hypercholesterolemic (HCh) subjects are characterized by a reduced number of glucocorticoid receptors (GcR) as compared with the cells of normolipidemics (N). Addition of HCh-sera or very low density lipoproteins, or low density lipoproteins isolated both from HCh-sera and N-sera to cultured human skin fibroblasts brought about a fall in the number of GcR in the cells. High density lipoproteins had no effect on GcR level. Dexamethasone was less effective in inhibiting cholesterol synthesis from [14C]acetate in the lymphocytes and fibroblasts with a reduced number of GcR. In the presence of dexamethasone (I x 10(-8)M) in fibroblast growth medium, reduced number of GcR (due to preincubation with very low density lipoproteins) led to a substantial increase in cholesterol synthesis. These findings indicate that the sensitivity of peripheral cells to glucocorticoids is decreased in HCh which might be one of the trigger mechanisms of atherogenesis.
Shakhov YuA
USSR Research Center for Preventive Medicine, Moscow.
Petrichenko
I E
IE
Chepurnenko
N V
NV
Perova
N V
NV
Oganov
R G
RG
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology*; D008074:Lipoproteins / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D005938:Glucocorticoids; D008074:Lipoproteins; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone