Kinetic parameters of the lipoprotein transport systems in the adrenal gland of the rat determined in vivo. Comparison of low and high density lipoproteins of human and rat origin

Abstract

These studies were done to characterize the rate of uptake of high (HDL) and low (LDL) density lipoprotein cholesterol by the adrenal gland of the rat under in vivo conditions. Animals were pretreated for 4 days with 4-aminopyrazolo[3,4-d]pyrimidine to essentially eliminate endogenous plasma lipoproteins and with aminoglutethimide for 1 h to block conversion of cholesterol to adrenal hormones. Such animals were then infused with varying amounts of HDL and LDL from both human and rat plasma, and this led to rapid accumulation of cholesterol, both free and esterified, in the adrenal glands over the subsequent 4-h period of observation. This uptake process was linear with respect to time and manifested saturation kinetics with respect to the steady state level of plasma lipoprotein cholesterol. When human lipoproteins were infused, the maximal rate of cholesterol uptake was approximately 0.45 mg/pair of adrenal glands/h for both HDL and LDL; however, the half-maximal rate of uptake (Km) was achieved at a plasma HDL cholesterol concentration of only 12 mg/dl while a concentration of 61 mg/dl was required to achieve the same velocity with LDL. When similar experiments were carried out with rat HDL, the Km equaled 7.2 mg/dl and a maximal rate of uptake of 0.32 mg/pair of adrenal glands/h was achieved. It was not possible to obtain complete kinetic curves using rat LDL, but at physiological plasma concentrations, there was no difference in the rate of cholesterol uptake from LDL of rat or human origin. When large amounts of both HDL (5.8 times Km) and LDL (3.1 times Km) were infused into the same animals, the rate of cholesterol uptake essentially equaled the sum of the maximal transport rates for the two lipoproteins. These data provide additional support for the concept that the adrenal gland (and ovary) of the rat can take up HDL and LDL cholesterol by separate mechanisms. However, from the quantitative data on the kinetics of these uptake processes, it is apparent that in this species HDL cholesterol must be the major substrate for the synthesis of adrenal hormones.