THE ENZYME INDUCERS 3-METHYLCHOLANTHRENE AND PHENOBARBITAL AFFECT THEACTIVITIES OF GLUCOCORTICOID HORMONE-REGULATED ENZYMES IN RAT-LIVER AND KIDNEY

3-Methylcholanthrene, an inducer of P448-type cytochromes (mostly 1A1 and 1A2), and phenobarbital, an inducer of P450-type cytochromes (most ly 2B1 and 2B2), are prototypical for the actions of many xenobiotics. They cause endocrine disruption by affecting, among others, steroid h ormone levels. Rats were treated with single bolus doses of 3-methylch olanthrene or phenobarbital, and enzyme activities that are controlled by glucocorticoids were measured in liver and kidney. The activities of the cytosolic enzymes L-alanine aminotransferase, indoleamine 2,3-d ioxygenase (L-tryptophan pyrrolase), phosphoenolpyruvate carboxykinase , L-serine dehydratase and L-tyrosine aminotransferase were affected i n a similar fashion: an initial activity reduction followed by two ove rshoots of activity 1 and 2 days after dosing. 3-Hydroxy-3-methylgluta ryl coenzyme A reductase, the microsomal key enzyme of sterol synthesi s, responded with a temporary reduction of activity only and evidently lost its diurnal rhythm. The time course of these changes is most lik ely caused by a combination of sub-physiological levels of glucocortic oids plus changes of other regulatory hormones elicited by feed intake , postprandial state, etc. A possible role for a combined action of th e arylhydrocarbon (Ah) and glucocorticoid receptors in the effects of 3-methylcholanthrene is also suggested. (C) 1998 Elsevier Science Irel and Ltd. All rights reserved.