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.