Acyl-coenzyme A: cholesterol acyltransferase and cholesterol ester hydrolase in the outer and inner cortices of the guinea pig adrenal: effects of adrenocorticotropin and dexamethasone.
The guinea pig adrenal cortex can be separated into two zones with contrasting lipid contents: a lipid-rich outer cortex and a lipid-poor inner cortex. Cytoplasmic lipid droplets contain cholesterol esters and are thought to act as a reservoir for steroid precursor. Such lipid droplets are numerous in the outer cortex, but accumulate in the inner region only after treatment with ACTH. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies cholesterol to fatty acids for storage in this pool, while cholesterol ester hydrolase (CEH) cleaves these esters, increasing free cholesterol. However, the relationship between intracellular cholesterol content and the activity of these enzymes is not clear. In this study we examine the capacity to esterify cholesterol (ACAT) and to hydrolyze cholesterol esters (CEH) in the lipid-rich and lipid-poor regions of the guinea pig adrenal in control animals and animals treated with ACTH or dexamethasone (DEX). For all conditions, the lipid-filled outer cortex possessed more ACAT and CEH activity than did the inner. Although ACAT and CEH in the outer cortex were relatively insensitive to ACTH compared to the enzymes in the inner zone, they were significantly suppressed after DEX treatment. This implies that in the basal state, ACAT and CEH may be almost maximally stimulated in the outer cortex, and that in these cells, cholesterol esterification and hydrolysis may occur at a high rate even in the basal state. The inner cortex responded to ACTH with increased ACAT activity, but was little affected by DEX. In the inner zone, CEH activity was not affected by ACTH or DEX. The lower level of these enzymes in the inner cortex correlates with the paucity of lipid droplets in these cells in the basal state, while the increase in ACAT, but not CEH, in this zone after ACTH treatment correlates with the accumulation of small lipid droplets in inner cortical cells of ACTH-treated animals.
Brody
R I
RI
Department of Cell Biology, New York University School of Medicine, New York 10016.
Black
V H
VH
D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D009928:Organ Specificity; D002787:Sterol Esterase / Q000378:metabolism*; D002785:Sterol O-Acyltransferase / Q000378:metabolism*
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D002265:Carboxylic Ester Hydrolases; D002787:Sterol Esterase