Stimulation of catalase synthesis and increase of carnitine acetyltransferase activity in the liver of intact female rats fed clofibrate

Administration of clofibrate (ethyl-α-p-chlorophenoxyisobutyrate) at dietary concentrations of 0.5%, 1% or2%, to intact female F-344 rats caused a significant increase in the hepatic catalase and carnitine acetyltransferase activities. Immunotitration experiments revealed that the increase in catalase activity was accompanied by a parallel increase in the amount of immuno logically reactive enzyme protein. Precursor incorporation experiments using [³H]-leucine and specific immunoprecipitation of newly synthesized catalase, indicated that the clofibrate induced increase in catalase protein could be accounted for by an increase in the relative rate of synthesis of this enzyme at induced steady state. The increase in the activities of catalase and carnitine acetyltransferase was accompanied by a profound increase in the number of peroxisomes in the liver cells. However, at 0.25% dose level clofibrate, as reported, had a minimal effect on hepatic peroxisomes and catalase in intact female rats. The increase in hepatic catalase, carnitine acetyltransferase, peroxisome number, and an 80,000 MW polypeptide in post-nuclear liver pellets in intact female rats treated with higher doses of clofibrate are similar to the changes observed in male rats fed this compound at 0.25% or 1% level. These studies demonstrate that the previously observed sex difference in the inducibility of enzymes associated with peroxisomes is obviated by increasing the dose of the inducer.