Essential fatty acid deficiency and adrenal cortical function

Adrenocortical cells were prepared from rats maintained on essential fatty acid-deficient diets and control litter mates. Cells from control rats had high concentrations of essential fatty acids in the cholesteryl ester fraction of which approximately 22% was arachidonate. In contrast, cells from EFA-deficient rats had only 2.5% arachidonate in the cholesteryl esters, even though the total esterified cholesterol level was comparable to that of controls. In place of the essential fatty acids, the cholesteryl esters of these cells were rich in 20:3 (n 9) and 22:3 ( n 9). When cells from EFA-deficient rats were incubated with ACTH or dibutyryl cyclic AMP, the output of corticosterone was the same as in controls. Also sterol esters were hydrolyzed to the same extent as in controls despite the unusual composition of the fatty acid esters. The phospholipids in both control and EFA-deficient cells contained high levels of arachidonate but were not hydrolyzed in either type of cell during incubation with ACTH or dibutyryl cyclic AMP. The results indicate that high levels of the prostaglandin precursors, namely linoleate and arachidonate, are not a sine qua non for the steroidogenic action of ACTH or cyclic AMP.Vahouny, G. V., V. A. Hodges, and C. R. Treadwell. Essential fatty acid deficiency and adrenal cortical function in vitro.]. Lipid Res. 1979. 20: 154-161. Supplementary key words cholesteryl ester hydrolysis * cyclic AMP . corticosterone . adrenal phospholipids * arachidonic acid prostaglandins . ACTH Rat adrenal cortex contains a high concentration of cholesteryl esters which are contained in numerous cytoplasmic inclusion droplets (1 -3). These esters represent a major metabolic precursor of the cholesterol required for steroidogenesis, and are extensively hydrolyzed in response to stress or ACTH administration in vivo (1 -3) or to ACTH in vitro (4). There is substantial evidence that the hydrolysis of adrenal sterol esters is a direct response to ACTH or cyclic AMP. It has been shown that ACTH will induce hydrolysis of cholesteryl esters even though further utilization of the released free cholesterol is blocked by cyclohexamide (5). Furthermore, it has recently been demonstrated that the enzyme responsible for this hydrolysis, sterol ester hydrolase (EC 3.1.1.13), is activated by a cyclic AMP-dependent protein kinase via a mechanism involving enzyme phosphorylation The cholesteryl esters of rat adrenal cortex have a high content of polyunsaturated acids, particularly arachidonate (9). Since these esters are extensively hydrolyzed during tropic hormone stimulation of the cortex (1 -4), it has been suggested that this lipid fraction may also serve as a reserve for the arachidonate substrate for prostaglandin synthesis (1 -3, IO). We have recently reported that exposure of rat adrenocortical cells to ACTH results in the specific formation of prostaglandin Ez, and that the major source of the arachidonate substrate for this synthesis is cholesterol arachidonate (1 1). Thus, the cholesteryl esters serve a dual role in providing a source of cholesterol for steroidogenesis and as precursor of a possible modulator of cyclic AMP formation and/or level (10). The levels of essential fatty acids, such as arachidonate, are substantially lower in adrenals of rats maintained on EFA-deficient diets (12, 13). These are largely replaced by unusual fatty acids, such as 20:3 (n 9) in the cholesteryl ester fraction (12, 13). Thus, it appears likely that, during stress or ACTH-induced hydrolysis of the cholesteryl esters in the adrenal cortex of EFA-deficient rats, there would be a lower concentration of free linoleate and arachidonate produced and a subsequent defect in prostaglandin formation. This might allow an assessment of the role of prostaglandins in the “steroidogenic cascade” of rat