Corticotropin increases the receptor-specific uptake of native low-density lipoprotein (LDL) - But not of oxidized LDL and native or oxidized lipoprotein(a) [Lp(a)] - In HEPG2 cells: No evidence for Lp(a) catabolism via the LDL-receptor

To understand the interaction of corticotropin (ACTH) and lipid catabolism, we analyzed the influence of ACTH on receptor-mediated lipoprotein uptake and compared the uptake and degradation of human native (RI LDL) and oxidized (Ox-LDL) low-density lipoprotein and native (N-Lp(a)) and oxidized (Ox-Lp(a)) lipoprotein(a) by human hepatoma (HepG2) cells. The receptor affinity of N-LDL, Ox-LDL, N-Lp(a), and Ox-Lp(a) was comparable (K-d, 33, 13, 24, and 13 mu g/mL medium), whereas the maximum degradative capacity was 10.5-fold higher in RI-LDL (V-max, 1,978 ng/mg cell protein) compared with Ox-LDL (189 ng/mg), In N-LDL, it was 4.5-fold higher than in N-Lp(a) (442 ng/mg) and eightfold higher than in Ox Lp(a) (246 ng/mg) (P <.05). Addition of ACTH to the cell cultures increased receptor-specific degradation of N-LDL by 44% (2,866 v 1,978 ng/mg, P<.05), whereas changes in Ox-LDL, N-Lp(a), and Ox-Lp(a) showed no significant increase. No differences in uptake specificity were observed with or without ACTH. In addition, a 12-hour preincubation of liver cells with LDL increased Lp(a) uptake by 40% to 50% with (411 v 620 ng/mg) and without (393 v 558 ng/mg) ACTH administration, These data indicate that ACTH elevates receptor-specific uptake of N-LDL, but only to a low extent versus Ox-LDL, N-Lp(a), or Ox-Lp(a), These results support the hypothesis that catabolism of oxidized lipoproteins and Lp(a) through the LDL receptor pathway is only a minor route of lipid metabolism, whereas LDL receptor activity itself can be stimulated by ACTH, Copyright (C) 1997 by W.B. Saunders Company.