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Journal of Lipid Research, Vol 32, 1611-1618, Copyright © 1991 by Lipid Research, Inc.
MM Prack, M Nicosia, DL Williams and J Gwynne
Among extrahepatic tissues the adrenal gland has one of the highest
concentrations of apoE mRNA and the highest rate of apoE synthesis. In the
present investigation several previously described in vivo treatments were
used to assess the relationship between apoE expression and cellular
cholesterol in the rat adrenal gland. Treatment of rats with
4-aminopyrazolo[3,4-d]pyrimidine (4-APP) to lower serum cholesterol
concentration and deplete adrenal gland cholesterol content decreased
adrenal gland apoE mRNA concentration. These adrenal responses were blocked
by dexamethasone (DEX) suggesting that the effect of 4-APP occurred
indirectly via stimulation of the adrenal gland by endogenous
adrenocorticotrophic (ACTH). Relative to control rats, DEX treatment
increased both adrenal gland cholesterol content and apoE mRNA
concentration. Concurrent ACTH and DEX administration reduced both adrenal
gland cholesterol content and apoE mRNA concentration relative to
DEX-treated rats. ACTH administration also rapidly decreased adrenal gland
apoE mRNA concentration and cholesterol content in rats pretreated with
DEX. In all the above experiments, adrenal gland cholesterol content and
apoE mRNA concentration were positively correlated (r = 0.78, P = 0.0001).
In contrast, aminoglutethimide treatment, which blocks adrenal gland
steroidogenesis and greatly increases adrenal gland cholesterol content,
was without effect on apoE mRNA concentration. ACTH administration to rats
treated with DEX + aminoglutethimide resulted in decreased adrenal apoE
mRNA despite greatly increased adrenal cholesterol content. This uncoupling
of adrenal gland cholesterol content and apoE mRNA concentration suggests
that apoE mRNA expression and cellular cholesterol are regulated
independently by ACTH.
ARTICLES
Relationship between apolipoprotein E mRNA expression and tissue cholesterol content in rat adrenal gland
Department of Pharmacological Sciences, State University of New York, Stony Brook 11794.
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