Altered adrenal gland cholesterol metabolism in the apolipoprotein E-deficient mouse

Fayanne E. Thorngate, Penelope A. Strockbine, Sandra K. Erickson, and David L. Williams

Pharmacological Sciences, University Medical Center, Stony Brook, NY 11794

Corresponding Author: Dave{at}pharm.sunysb.edu

Previous studies suggest the hypothesis that apoE produced by adrenocortical cells modulates cellular cholesterol metabolism to enhance the storage of EC at the expense of cholesterol delivery to the steroidogenic pathway. In the present study parameters of adrenal cholesterol metabolism and corticosteroid production were examined in wild type and apoE-deficient (apoe-/- ) mice. Adrenal gland EC content and the EC/FC ratio in mice stressed by ACTH treatment or saline injection were reduced in apoe-/- compared to apoe+/+ mice. Relative to apoe+/+ mice, apoE deficiency also resulted in increased levels of plasma corticosterone in the basal state, in response to acute or long-term ACTH treatment, and after a swim-induced neuroendocrine-directed stress test. Measurements of adrenal gland SR-BI, LDL receptor, and LRP levels and the activities of ACAT or HMG CoA reductase showed no difference between genotypes. Apoe-/- and apoe+/+ mice showed similar quantitative increases in LDL receptors, SR-BI, adrenal weight gain, and ACAT activities in response to ACTH, and both genotypes had similar basal plasma ACTH concentrations. These results suggest that the effects of apoE deficiency reflect events at the level of the adrenal gland and are specific to changes in cholesterol accumulation and corticosterone production. Further, these findings support the hypothesis that apoE acts to enhance adrenocortical EC accumulation and diminish corticosterone production.

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