ACTH induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase, cholesterol biosynthesis, and steroidogenesis in primary cultures of bovine adrenocortical cells.
The current studies demonstrate that corticosteroidogenesis can be maintained by primary cultures of bovine adrenocortical cells under lipoprotein-depleted conditions. The cholesterol necessary as substrate for steroid synthesis was found to arise from de novo synthesis within these cells. Adrenocorticotropin (ACTH) increased 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity 5-fold within 12 h after addition to the medium. The increase in activity apparently represented accumulation of enzyme as determined by protein blotting and immunodetection. The predominant immunodetectable species of HMG-CoA reductase from bovine adrenal cells was 97,000 daltons; no higher molecular mass species was detectable. The ACTH induction of HMG-CoA reductase activity could be prevented after inhibition of cholesterol conversion to pregnenolone with clotrimazole. These results are suggestive that ACTH increases adrenocortical cholesterol biosynthesis and HMG-CoA reductase activity after conversion of a cellular pool of cholesterol and/or oxysterol into steroid. The increased rate of cholesterol biosynthesis is then capable of maintaining ACTH-promoted steroid production. This is the first study, in vitro, to demonstrate an ACTH-promoted accumulation of HMG-CoA reductase of adrenocortical cells.
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D011284:Pregnenolone / Q000378:metabolism
D000085:Acetates; D000305:Adrenal Cortex Hormones; D002250:Carbon Radioisotopes; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D019342:Acetic Acid