ACTH decreases the expression and secretion of apolipoprotein B in HepG2 cell cultures.
Administration of adrenocorticotropic hormone (ACTH) has been shown to decrease plasma concentrations of apolipoprotein B (apoB) containing lipoproteins, including lipoprotein(a), in man. However, the mechanism behind this hypolipidemic effect is unknown. This study aimed at distinguishing between the main possibilities (increased elimination or decreased production of lipoproteins) using HepG2 cell cultures. Addition of ACTH to the cell culture medium selectively down-regulated apoB mRNA expression and apoB secretion in a dose-dependent manner. At 100 pmol/liter ACTH, the apoB mRNA level was about 40% lower than in the untreated cells, and the secretion of apoB into the medium was decreased to a similar extent. The expression and secretion of other apolipoproteins (apoA-I, apoE, and apoM), however, were not affected by ACTH. Under normal culture conditions the level of secretion of apoB from HepG2 cells is quite low. In the presence of 0.4 mmol/liter oleic acid secretion of apoB increased 3-fold, but this phenomenon was not seen in ACTH-treated cells. Binding and internalization of radiolabeled low density lipoprotein (LDL) by HepG2 cell, as well as LDL-receptor mRNA and scavenger receptor B-I mRNA levels, were not influenced by ACTH. In conclusion, ACTH directly and selectively down-regulated the production and secretion of apoB in HepG2 cell cultures, suggesting that a principal mechanism behind the cholesterol-lowering effect of ACTH in vivo may be a decreased production rate of apoB-containing lipoproteins from the liver.
Xu
N
N
Department of Clinical Chemistry, Institute of Laboratory Medicine, University Hospital of Lund, S-221 85 Lund, Sweden.
Ekstrom
U
U
Nilsson-Ehle
P
P
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D001053:Apolipoproteins / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism*; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D001053:Apolipoproteins; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D019301:Oleic Acid; D012313:RNA; D000324:Adrenocorticotropic Hormone