Factors which may be significant regarding regulation of the clofibrate-dependent induction of hepatic peroxisomal beta-oxidation and hepatomegaly.

The stimulation of hepatic polyamine metabolism observed 5 hr following intraperitoneal injection of clofibrate to rats was completely abolished following prior treatment with alpha-difluoromethylornithine. No induction of peroxisomal beta-oxidation could be observed 5 hr after injection of clofibrate, although appreciable induction occurred 10 hr after injection. Prior treatment with difluoromethylornithine partially inhibited this induction. On chronic treatment with clofibrate together with difluoro-methylornithine, clofibrate-dependent induction of peroxisomal beta-oxidation, as well as of the hepatomegaly, was partially inhibited. In hypophysectomized rats, no stimulation of polyamine metabolism was found following acute administration of a single dose of clofibrate. In thyroidectomized and in adrenalectomized animals, this stimulation was apparent, although the levels of activity were only some 10% of control levels. In hypophysectomized, in thyroidectomized and in adrenalectomized rats, appreciable induction of peroxisomal beta-oxidation occurred on chronic treatment with clofibrate. However, no hepatomegaly was observed in these animals.