Differential effects of altered hormonal state on the induction of ACYL-CoA hydrolases and peroxisomal β-oxidation by clofibric acid

Abstract

Induction of hydrolase I, hydrolase II, peroxisomal β-oxidation and hepatomegaly caused by clofibric acid ( p-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 β-oxidation were induced to a similar extent, compared to those of intact rats. (2) In hypothyroid rats, induction of hydrolase I, hydrolase II, peroxisomal β-oxidation and hepatomegaly was reduced. In hyperthyroid rats, the ability to induce hydrolase I, hydrolase II and peroxisomal β-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 β-oxidation was induced normally. Differences in the response of four parameters (hydrolase I, hydrolase II, peroxisomal β-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).