Sources of Extramitochondrial Corticoidogenic Cholesterol in the Adrenal Cortex

• Published in: Japanese journal of pharmacology 1985, Vol.38(2), pp.207-214
• Main Authors: IWAKI, Takamasa, NOGUCHI, Akibumi, SEKIMOTO, Takehito
• Format: Article
• Language: English
• Subjects: Adrenal Cortex - metabolism; Adrenal Cortex Hormones - biosynthesis; Adrenocorticotropic Hormone - pharmacology; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Calcium - pharmacology; Cattle; Chloroquine - pharmacology; Cholesterol - analysis; Cholesterol - metabolism; Cricetinae; Cycloheximide - pharmacology; Dichlorvos - pharmacology; Female; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Lovastatin - analogs & derivatives; Male; Mesocricetus; Naphthalenes - pharmacology; Other biological molecules; Rats; Rats, Inbred Strains; Species Specificity; Sulfonamides - pharmacology; Terpenes, steroids. Hormones
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.38.207

Intracellular sources of extramitochondrial corticoidogenic cholesterol in bovine, rat and hamster adrenocortical cells were examined in vitro by comparing the species differences in the effects of various inhibitors on the adrenocorticotropic .hormone (ACTH)-induced corticoidogenesis. The inhibitors were ML-236B (3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor), W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide; calmodulin inhibitor), dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate; organic phosphorylation inhibitor), chloroquine ((7-chloro-4-4-diethylamino-1-methyl-butylamino) quinoline; lysosomal enzyme inhibitor) and cycloheximide (protein synthesis inhibitor). During 2 to 3 hr incubation periods, the ACTH-induced corticoidogenesis was not inhibited by ML-236B (100 μM) in the bovine and rat adrenocortical cells. In the hamster adrenocortical cells, ML-236B (100 μM) did not affect the ACTH-induced corticoidogenesis during the initial 1 hr incubation periods; but thereafter, the ACTH-induced corticoidogenesis during the subsequent 2 hr incubation periods was completely blocked by ML-236B. The ACTH-induced corticoidogenesis was inhibited by W-7 (up to 25 μM) in the bovine and rat adrenocortical cells, but this was not the case in the hamster cells. Chloroquine (up to 400 aM) inhibited the ACTH-induced corticoidogenesis in the adrenocortical cells of three different species, but the hamster adrenal cells were much more vulnerable than the bovine and rat cells. The ACTH-induced corticoidogenesis in the adrenocortical cells of three different species were equally inhibited by cycloheximide (up to 1 mM). It could be deduced from the present data that intracellular sources of corticoidogenic cholesterol during the ACTH-induced corticoidogenesis in vitro are mainly lysosomes and de novo synthetized cholesterol in the hamster cells, and the main sources are lipid droplets and lysosomes in the rat and bovine cells, respectively.