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

Treatment with adrenocorticotrophic hormone (ACTH) has a well-documented cholesterol-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. Since apolipoproteins are important determinants of lipoprotein metabolism, we sought to extend the knowledge of the effect of ACTH treatment on the serum apolipoprotein (apo) pattern. Twelve healthy individuals and 14 dyslipoproteinemic hemodialysis patients were recruited. The two groups responded similarly to ACTH1-24 at the dose of 1 mg daily for four days. In accordance with previous results, serum concentrations of total cholesterol decreased 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 concentrations 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. Moreover, in the healthy individuals, the serum concentrations of apo CIII did not change in response to ACTH, whereas in the hemodialysis patients, those of apo CIII not associated with apo B increased significantly by 44%. Since apo E binds strongly to the LDL receptor, the present results suggest that the cholesterol-lowering effect of ACTH may be mediated by facilitated hepatic uptake of apo E-enriched apo B-containing lipoproteins. Thus, the findings stimulate further research.