Differential effects of altered hormonal state on the induction of acyl-CoA hydrolases and peroxisomal beta-oxidation by clofibric acid.
Induction of hydrolase I, hydrolase II, peroxisomal beta-oxidation and hepatomegaly caused by clofibric acid (rho-chlorophenoxyisobutyric acid) administration was investigated in relation to alterations in hormonal state of glucocorticoid, thyroid hormone and insulin. (1) In adrenalectomized rats, the ability to induce hydrolase I was depressed effectively and little hepatomegaly was produced. Hydrolase II and peroxisomal beta-oxidation were induced to a similar extent, compared to those of intact rats. (2) In hypothyroid rats, induction of hydrolase I, hydrolase II, peroxisomal beta-oxidation and hepatomegaly was reduced. In hyperthyroid rats, the ability to induce hydrolase I, hydrolase II and peroxisomal beta-oxidation was depressed, although hepatomegaly was produced by the same or a greater extent as in intact rats. (3) In diabetic rats, marked reduction of ability to induce both hydrolase I and II was observed and induction of hepatomegaly was depressed slightly, although peroxisomal beta-oxidation was induced normally. Differences in the response of four parameters (hydrolase I, hydrolase II, peroxisomal beta-oxidation and liver size) to alterations in hormonal state suggest that the four biological responses to clofibric acid may each be mediated through distinct mechanism(s) other and regulated by distinct hormone(s).
D000315:Adrenalectomy; D000818:Animals; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006529:Hepatomegaly / Q000378:metabolism; D006980:Hyperthyroidism / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D009940:Organoids / Q000378:metabolism*; D010084:Oxidation-Reduction; D010170:Palmitoyl-CoA Hydrolase / Q000096:biosynthesis*; D051381:Rats; D013869:Thiolester Hydrolases / Q000096:biosynthesis*
D005227:Fatty Acids; D007328:Insulin; D002995:Clofibric Acid; D003907:Dexamethasone; D013869:Thiolester Hydrolases; D010170:Palmitoyl-CoA Hydrolase; D002994:Clofibrate