Uptake,Hydrolysis and Synthesis of Cholesterol Esters by a Transplantable Adrenal Cortical Tumor. ∗

Abstract

Summary

A very low-density, cholesterol-labeled lipoprotein fraction of rat chyle, in which about 70% of the sterol C¹⁴ was in the esterified form, was injected intravenously into normal rats and into rats bearing the transplanted Snell adrenal cortical tumor 494H. The esterified and free sterol C¹⁴ contents of the tumor and of the normal adrenal glands were measured at several intervals after the injection. The same general pattern—an initial decrease followed by an increase in the proportion of sterol C¹⁴ esterified—was observed for tumor and normal gland. This suggests that in both cases the uptake and hydrolysis of labeled chyle cholesterol esters were followed by cholesterol reesterification. In the tumor, however, the hydrolysis occurred later and the subsequent reesterification was much less pronounced. A comparison of esterification of free cholesterol and hydrolysis of cholesterol oleate by homogenates prepared from tumors and normal glands revealed the following for both tissues: The pH optimum, in the absence of cofactors, was 5.0. Addition of CoA, ATP, Mg⁺⁺ and GSH at that pH did not increase the esterification, whereas their addition at pH 6.6 did. Hydrolysis of cholesterol oleate was highest at pH 7.0 or above. Quantitative differences between the tumor and the normal adrenal in vitro reflected differences observed in vivo. Homogenates prepared from the tumor had a lower capacity for hydrolyzing cholesterol oleate and for esterifying free cholesterol than did homogenates of the normal gland. In the tumor, in contrast to the normal adrenal, the predominant form of the endogenous sterol was the free rather than the esterified. This finding, as well as those cited above, suggests that the major of the two described defects in cholesterol metabolism in the tumor is the impairment in capacity to esterify free cholesterol.