Hepatic microsomal induction in rat liver: heterogeneity of response

The concept that urinary 6-hydroxycortisol excretion patterns reflect all microsomal enzyme activities remains a subject of controversy. Three different microsomal hydroxylase activities were therefore studied in rat liver after the animals were intoxicated with alcohol, phenobarbital, or a combination thereof. The activities of pentobarbital hydroxylase, aniline hydroxylase, and cortisol 6-hydroxylase (the enzyme metabolizing cortisol to 6-hydroxycortisol) were assayed simultaneously after each treatment. A heterogeneity of enzyme activities was noted. Cortisol 6-hydroxylase activity did not parallel the activity patterns of the two other hydroxylases. The data suggest that before urinary 6-hydroxycortisol excretion patterns can be utilized as an index of microsomal enzyme induction, the effect of the specific drug on individual cytochrome P-450 hydroxylases is required.