Adrenocorticotrophic hormone retarded metabolism of low-density lipoprotein in rats.

In humans, treatment with adrenocorticotrophic hormone (ACTH) has well-documented plasma cholesterol lowering and low-density lipoprotein (LDL) lowering effects. Moreover, it has recently been demonstrated that ACTH directly inhibits apolipoprotein B expression and secretion in the HepG2 cell line. The aim of the present study was to demonstrate the effects of ACTH on lipid metabolism in the rat, and particularly on LDL metabolism. Rats were treated with porcine ACTH for 3 days and plasma lipid parameters were determined. Surprisingly, the total cholesterol level and LDL-cholesterol level were increased in plasma after ACTH administration, displaying an opposite effect of ACTH in humans. Furthermore, clearance and distribution of radiolabeled human LDL in different tissues were investigated in the rat after ACTH treatment. The clearance of radiolabeled LDL was slightly decreased after ACTH treatment suggesting that ACTH can inhibit LDL catabolism in the rat. Unlike previous observations performed in human hepatic cell cultures, there was no change in apoB expression in rat liver, or in apoE and apoM expression, after treatment with ACTH. This study clearly demonstrates that ACTH has species specificity differences in humans and in the rat.