Increased turnover of the messenger RNA encoding tyrosine aminotransferase can account for the desensitization and de‐induction of tyrosine aminotransferase by 8‐bromo‐cyclic AMP treatment and removal.

Treatment of H‐4 rat hepatoma cells with 8‐bromo‐cyclic AMP (8‐Br‐cAMP) resulted in a transient induction of the gluconeogenic enzyme tyrosine aminotransferase. Synthesis of tyrosine aminotransferase and the level of its corresponding mRNA peaked 2 h after the addition of the cyclic nucleotide and declined thereafter. Tyrosine aminotransferase synthesis and mRNA failed to respond to the readdition of fresh 8‐Br‐cAMP, a process which we defined as desensitization. Removal of 8‐Br‐cAMP resulted in a decrease in tyrosine aminotransferase synthesis and mRNA, a process defined as de‐induction. The relative transcription rate of the tyrosine aminotransferase gene and the turnover of its mRNA were determined by labeling intact cells with [3H]uridine. 8‐Br‐cAMP led to an increase in the rate of tyrosine aminotransferase transcription which was sustained for at least 4 h. The transcription rate declined upon de‐induction. In addition, 8‐Br‐cAMP increased the turnover rate of tyrosine aminotransferase mRNA, but only after a 1.5‐3 h time lag. This increased degradation rate persisted for at least 1.5 h after the removal of 8‐Br‐cAMP. These two contrasting and temporally distinct processes could account for the observed changes in tyrosine aminotransferase mRNA levels in response to 8‐Br‐cAMP treatment and removal.