On the role of intra-adrenal unesterified cholesterol in the steroidogenic effect of corticotropin.
Since ACTH (corticotropin) increases intra-adrenal and intramitochondrial free cholesterol levels, the relative importance of these effects during ACTH-induced steroidogenesis was examined. Rats were treated in vivo with ACTH plus aminoglutethimide to increase free cholesterol (2--3-fold), and the latter was tested as a steroidogenic factor after removal of aminoglutethimide blockade and subsequent prolonged incubation of the cholesterol-rich adrenal sections in vitro. The increased free cholesterol served as a positive steroidogenic factor only during the early phase of the incubation when other ACTH-induced steroidogenic factors were operative. At later times of incubation, the increased free cholesterol did not, of itself, enhance steroidogenesis unless ACTH was added. These results suggest that the ACTH-induced enhancement of intraadrenal (and mitochondrial) free cholesterol may be important in determining the amount of steroids produced in response to a given ACTH stimulus, but another ACTH-induced factor is more important in initiating the steroidogenic process. This factor (? labile protein) appears to control a metabolic process which is distal to the mitochondrial uptake of free cholesterol.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000616:Aminoglutethimide / Q000494:pharmacology*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003345:Corticosterone / Q000096:biosynthesis*; D007700:Kinetics; D008297:Male; D051381:Rats
D000616:Aminoglutethimide; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D003345:Corticosterone