Regulation of rat-liver tyrosine-aminotransferase mRNA by hydrocortisone and by N6,O2'-dibutyryladenosine 3',5'-phosphate.

The intraperitoneal injection of either hydrocortisone of N6,O2'-dibutyryladenosine 3',5'-phosphate (Bt2cAMP) results in a specific increase in functional tyrosine aminotransferase mRNA (mRNATAT) activity in rat liver that is proportional to the degree of enzyme induction. Both require continuous RNA synthesis. There are several differences in the response to these inducers: (a) the magnitude of the increase is greater following hydrocortisone injection than after Bt2cAMP; (b) the peak response is seen within 1 h following the injection of Bt2cAMP as compared to the 5 h required for the maximal response following hydrocortisone injection; (c) finally, although both responses are rapid, the lag period which precedes the accumulation of functional tyrosine aminotransferase mRNA activity following the injection of hydrocortisone is at least 20 min whereas following Bt2cAMP it is 5-10 min. The administration of actinomycin D to rats 5 h after they were treated with hydrocortisone causes an additional twofold increase in tyrosine aminotransferase enzymatic activity, a phenomenon known as superinduction, but does not prevent the normal decrease in its mRNA seen at this time. This dissociation of enzyme and mRNA activities indicates that superinduction of tyrosine aminotransferase is not due to a selective stabilization of the mRNA which codes for this protein.