Effects of short-term treatment with corticotropin on the serum apolipoprotein pattern

Treatment with adrenocorticotrophic hormone (ACTH) has a well-documented ch olesterol-lowering effect. Increased uptake of low-density lipoprotein (LDL ) by HepG2 cells in response to incubation with ACTH has been demonstrated but the precise cholesterol-lowering mechanism has resisted elucidation. Si nce apolipoproteins are important determinants of lipoprotein metabolism, w e sought to extend the knowledge of the effect of ACTH treatment on the ser um apolipoprotein (apo) pattern. Twelve healthy individuals and 14 dyslipop roteinemic hemodialysis patients were recruited. The two groups responded s imilarly to ACTH(1-24) at the dose of 1 mg daily for four days. In accordan ce with previous results, serum concentrations of total cholesterol decreas ed by 18% and 17%, LDL cholesterol by 25% and 30%, and apo B by 20% and 19% , respectively, while there were no significant changes in the serum concen trations of triglycerides, high-density lipoprotein cholesterol and apo AI. Novel findings were that the serum concentrations of total apo E increased by 48% and 31%, and apo B-associated apo E by 69% and 46% respectively. Mo reover, in the healthy individuals, the serum concentrations of apo CIII di d not change in response to ACTH, whereas in the hemodialysis patients, tho se of apo CIII not associated with apo B increased significantly by 44%. Si nce apo E binds strongly to the LDL receptor. the present results suggest t hat the cholesterol-lowering effect of ACTH may be mediated by facilitated hepatic uptake of apo E-enriched apo B-containing lipoproteins. Thus, the f indings stimulate further research.