Stimulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity by o,p'-DDD.
To investigate the mechanism by which o'p'-DDD (2,2-bis [2-chlorphenyl-4-chlorophenyl]-1,1-dichloroethane; Mitotane) produces hypercholesterolemia in man, we studied the effect of the drug on hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity in reverse light-cycled rats. o,p'-DDD markedly stimulated reductase activity in vivo and in vitro in a dose-dependent manner. This effect was not associated with demonstrable adrenocortical toxicity or changes in plasma corticosterone concentrations. Thus o,p'-DDD may elevate circulating cholesterol levels in man by increasing endogenous cholesterol synthesis. In addition, the o,p'-DDD may elevate circulating cholesterol levels in man by increasing endogenous cholesterol synthesis. In addition, the o,p'-DDD-treated rat may serve as a useful model for testing other agents for the ability to suppress endogenous cholesterol synthesis and lower circulating cholesterol levels.
D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003345:Corticosterone / Q000097:blood; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D008939:Mitotane / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains
D008939:Mitotane; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D003345:Corticosterone