Effect of long-term inhibition of hydroxy-methylglutaryl coenzyme A reductase by mevinolin on the zona fasciculata of rat adrenal cortex. A combined morphometric and biochemical study.
The effects of a 7-day infusion with mevinolin, a potent competitive inhibitor of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase, on the adrenal zona fasciculata were examined in normal and dexamethasone/ACTH-treated rats. In both groups of animals, the drug caused a lowering in plasma and intra-adrenal cholesterol concentrations, as well as a slight decrease in the blood level of corticosterone. Morphometry of zona fasciculata cells showed that specific mevinolin-induced changes (i.e. those occurring in both groups of rats and therefore not due to enhanced release of ACTH following decrease in circulating corticosterone) are severe lipid-droplet depletion and a conspicuous increase in smooth endoplasmic reticulum (SER) and peroxisomes. The hypothesis is discussed that these morphological changes express a compensatory response of zona fasciculata cells to counteract the mevinolin-induced inhibition of cholesterol synthesis in both liver and adrenal cortex.
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D008148:Lovastatin; D003345:Corticosterone