Sources of extramitochondrial corticoidogenic cholesterol in the adrenal cortex.
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 microM) in the bovine and rat adrenocortical cells. In the hamster adrenocortical cells, ML-236B (100 microM) 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 microM) in the bovine and rat adrenocortical cells, but this was not the case in the hamster cells. Chloroquine (up to 400 microM) 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Iwaki
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T
Noguchi
A
A
Sekimoto
T
T
D000302:Adrenal Cortex / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002738:Chloroquine / Q000494:pharmacology; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D004006:Dichlorvos / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008148:Lovastatin / Q000031:analogs & derivatives*; D008297:Male; D008647:Mesocricetus; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013449:Sulfonamides / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D009281:Naphthalenes; D013449:Sulfonamides; C012258:mevastatin; C017967:W 7; D004006:Dichlorvos; D002738:Chloroquine; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D003513:Cycloheximide; D008148:Lovastatin; D002118:Calcium