ACTH decreases the expression and secretion of apolipoprotein B in HepG2 cell cultures

Administration of adrenocorticotropic hormone (ACTH) has been shown to decr ease plasma concentrations of apolipoprotein B (apoB) containing lipoprotei ns, including lipoprotein(a), in man. However, the mechanism behind this hy polipidemic effect is unknown. This study aimed at distinguishing between t he main possibilities (increased elimination or decreased production of lip oproteins) using HepG2 cell cultures. Addition of ACTH to the cell culture medium selectively downregulated apoB mRNA expression and apoB secretion in a dose-dependent manner. At 100 pmol/liter ACTH, the apoB mRNA level was a bout 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 affect ed 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 AC TH-treated cells. Binding and internalization of radiolabeled low density l ipoprotein (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 apo B in HepG2 cell cultures, suggesting that a principal mechanism behind the cholesterol-lowering effect of ACTH in vivo may be a decreased production r ate of apoB-containing lipoproteins from the liver.