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.
D012437:Adenosylmethionine Decarboxylase / Q000032:analysis; D000315:Adrenalectomy; D000818:Animals; D002994:Clofibrate / Q000633:toxicity*; D000518:Eflornithine; D006529:Hepatomegaly / Q000139:chemically induced*; D007016:Hypophysectomy; D008099:Liver / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000032:analysis; D010084:Oxidation-Reduction; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy
D011073:Polyamines; D009952:Ornithine; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D002994:Clofibrate; D000518:Eflornithine