Abstract
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.
Highlights
Among extrahepatic tissues the adrenal gland has one of the highest concentrations of apolipoprotein E (apoE) mRNA and the highest rate of apoE synthesis
Relationship between adrenal gland cholesterol content and apoE mRNA concentration In order to assess the relationship between adrenal cholesterol and apoE mRNA levels, rats were treated in vivo with several agents known to alter adrenal steroidogenesis and/or cholesterol content
Adrenal gland cholesterol stores are severely depleted in 4-APP-treated rats because ACTHstimulated steroidogenesis occurs in the absence of sufficient serum lipoprotein cholesterol to serve as substrate for glucocorticoid production [18, 31]
Summary
Among extrahepatic tissues the adrenal gland has one of the highest concentrations of apoE mRNA and the highest rate of apoE synthesis. Treatment of rats with 4-timinopyrazolo[3,4-djpyrimidine (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). ACTH administration to rats treated with DEX + aminoglutethimide resulted in e 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.-Prack, M.
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