Rat adrenal uptake and metabolism of high density lipoprotein cholesteryl ester

Metabolism of high density lipoprotein (HDL) cholesteryl ester (CE) by cultured rat adrenal cells was studied. Addition of 3HCE-HDL to cells pretreated with adrenocorticotrophin in lipoprotein poor media resulted in a time- and concentration-dependent accumulation of 3Hcholesteryl ester and production of 3Hcholesterol and 3Hcorticosterone. HDL-CE metabolism could be described as the sum of a high affinity ( HDL-cholesterol1/2 max = 16 micrograms/ml) and low affinity ( HDL-cholesterol1/2 max greater than 70 micrograms/ml) process. 3HCholesterol was found both intracellularly and in the media. Accumulation of 3Hcholesteryl ester could not be attributed to uptake and re-esterification of unesterified cholesterol since addition of Sandoz 58-035, an inhibitor of acyl coenzyme A:cholesterol acyltransferase, did not prevent ester accumulation. Moreover, addition of chloroquine did not inhibit cholesteryl ester hydrolysis indicating that hydrolysis was not lysosomally mediated. Aminoglutethimide prevented conversion of 3HCE-HDL to steroid hormones but did not inhibit 3Hcholesteryl ester uptake. Cellular accumulation of 3H cholesteryl ester exceeded accumulation of 125I-apoproteins 5-fold at 1 h and 35-fold at 24 h indicating selective uptake of cholesteryl ester moiety. We conclude that rat adrenal cells possess a mechanism for selective uptake of HDL cholesteryl esters which provides substrate for steroidogenesis. These results constitute the first direct demonstration that cholesteryl esters in HDL can be used as steroidogenic substrate by the rat adrenal cortex.