Differential Effects of Glucocorticoids and Adenosine 3',5'-Monophosphate on Hepatic Enzyme Synthesis

The processes involved in the induction of the liver enzyme tyrosine transaminase by either hydrocortisone or adenosine 3',5'-monophosphate (cyclic AMP) in organ culture have been shown to exhibit different characteristics. Removal of cyclic AMP, as the N6,O2'-dibutyryl analogue (dibutyryl cyclic AMP) during the early phase of induction of either tyrosine transaminase or phosphoenolpyruvate carboxykinase, or after attainment of a new elevated steady state level, prompted a virtually immediate cessation of the induction process. In contrast, removal of hydrocortisone at either stage did not stop elevation of transaminase activity for 1½ to 2 hours even in the presence of actinomycin D. The sequential addition of one inducer after maximal induction by the other revealed that hydrocortisone markedly amplified the subsequent effect of dibutyryl cyclic AMP on the transaminase. Prior exposure to dibutyryl cyclic AMP did not lead to any amplification of the subsequent enzyme response to hydrocortisone. The results are interpreted to indicate that hydrocortisone and cyclic AMP act at sequential sites n the synthesis of tyrosine transaminase. The suggestion s made that cyclic AMP may act at a post-transcriptional evel in the case of both the transaminase and carboxykinase.