[Reduced cell sensitivity to glucocorticoid hormones in hypercholesterolemia].
The number of 3H-dexamethasone binding sites in lymphocytes of subjects with hypercholesterolemia (HCS) was found to be decreased as compared to the receptor level in normolipidemic patients (N). In HCS-lymphocytes, the dexamethasone-induced inhibition of 3H-thymidine and 14C-acetate incorporation was less pronounced (by 20% and 22%, respectively) than in control cells, which is suggestive of the decreased sensitivity of HCS-lymphocytes to the hormone. An addition of 5-25% HCS blood sera to human skin fibroblast cultures caused a 10-50% decrease in the number of 3H-dexamethasone binding sites and diminished the Kd values 2-3 times. Lipid-depleted HCS-sera had no effect on the glucocorticoid reception in fibroblasts, whereas very low (VLDL) and low (LDL) density lipoproteins inhibited the 3H-dexamethasone binding to the cells. The most potent inhibiting effect was exerted by VLDL (both N-VLDL and HCS-VLDL). HCS-VLDL were more effective than N-LDL. HCS-HDL and N-HDL did not effect the 3H-dexamethasone binding to fibroblasts. In cells preincubated with VLDL dexamethasone inhibited the incorporation of 3H-thymidine and 14C-acetate less intensively (by 27% and 20%, respectively) than in control fibroblasts. The experimental results are suggestive of a decreased sensitivity of peripheral HCS-cells to glucocorticoids, which may shed some light on the mechanism of hypercholesterolemia realization into coronary heart disease and atherosclerosis.
Shakhov
Iu A
IuA
Petrichenko
I E
IE
Chepurnenko
N V
NV
Sokolova
M A
MA
Medvedeva
L A
LA
D000328:Adult; D001667:Binding, Competitive; D002478:Cells, Cultured; D003327:Coronary Disease / Q000209:etiology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000378:metabolism*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D012307:Risk Factors
D008055:Lipids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone
Snizhenie kletochnoĭ chuvstvitel'nosti k gliukokortikoidnym gormonam pri giperkholesterinemii.