DIRECT EFFECTS OF CORTICOTROPIN ON PLASMA-LIPOPROTEIN METABOLISM IN MAN - STUDIES IN-VIVO AND IN-VITRO

To explore the roles of corticotropin and corticosteroids in the regulation of plasma lipoprotein concentrations, we investigated the effects of 4 days' administration of corticotropin 1-24 (Synacthen Depot, CIBA-Geigy, Basel, Switzerland) in healthy volunteers and compared them with those occurring during treatment with a synthetic glucocorticoid (dexamethasone). Corticotropin administration resulted in rapid decreases of apolipoprotein (apo) B, low-density lipoprotein (LDL) cholesterol, and plasma triglyceride concentrations of 20% to 30%, whereas dexamethasone treatment did not affect any of the apo B-containing lipoproteins. Lipoprotein (a) [Lp (a)] level was decreased by about 30%; in this case, a similar reduction was noted after dexamethasone treatment. High-density lipoprotein (HDL) concentrations increased with both treatments; however, apo A-I concentrations increased only with glucocorticoid treatment, whereas HDL cholesterol level was elevated after both regimens. The activity of hepatic lipase (HL) was significantly decreased after corticotropin, but not after glucocorticoid treatment. LDL receptor activity, studied in cultured Hep G2 cells, was upregulated by about 30% after incubation with corticotropin. We conclude that corticotropin exerts direct effects on lipoprotein metabolism in man, primarily on apo B-containing lipoproteins, which decrease probably due to a corticotropin-mediated upregulation of LDL receptor activity. The metabolism of Lp (a) seems to be primarily influenced by corticosteroids, which rapidly decrease Lp (a) concentrations. An inhibitory effect of corticotropin on HL activity seems to contribute, besides glucocorticoid effects on apo A-I metabolism, to the increase in HDL level. © 1994.