Glucocorticoids upregulate high-affinity, high-density lipoprotein binding sites in rat hepatocytes.
Glucocorticoid hormones (GL) regulate high-density lipoprotein (HDL) plasma concentrations by increasing synthesis and secretion of HDL by the liver. However, little is known about the effect of GL on the uptake and processing of HDL by hepatocytes (HEP). To investigate this question, we studied the effects of dexamethasone (DEX) on the expression of high-affinity HDL-binding sites via the specific binding and internalization of iodine-labeled apolipoprotein E (apo E)-free HDL3 in a culture of rat HEP. Specific binding and internalization of HDL3 decreased by 60% in cells cultured in the absence of DEX for 48 hours. At concentrations of 10(-7) and 10(-5) mol/L, DEX prevented the decrease, maintaining specific binding and internalization versus the control level (at 24 hours). HDL-binding sites with a Kd of 20 micrograms/mL were revealed on the surface of cultured HEP. HEP demonstrated a greater binding capacity in the presence of DEX at concentrations of 10(-7) and 10(-5) mol/L (125 v 45 ng/mg cell protein). The effect of the hormone has demonstrated to be dose-dependent at concentrations between 10(-9) and 10(-7) mol/L, leveling off at 10(-7). Higher concentrations did not induce a further increase in specific binding and internalization. Withdrawal of the hormone from culture medium was associated with a decrease in specific binding of the ligand by 60% in the following 24 hours. To investigate the effect of glucocorticoid deficiency on liver uptake of HDL in vivo, specific binding and internalization were studied in a culture of HEP isolated from adrenalectomized rats (AER) at 2 hours after seeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Bocharov
A V
AV
Cardiology Research Center, Moscow, Russia.
Huang
W
W
Vishniakova
T G
TG
Zaitseva
E V
EV
Frolova
E G
EG
Rampal
P
P
Bertolotti
R
R
D000315:Adrenalectomy; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D008075:Lipoproteins, HDL; D003907:Dexamethasone; D002784:Cholesterol; D003513:Cycloheximide; D008148:Lovastatin