Time course of the changes of TH mRNA in rat brain and adrenal medulla after a single injection of reserpine.

A single injection of reserpine causes a long lasting enhancement of the activity of tyrosine hydroxylase (TH), the enzyme catalyzing the rate-limiting step in the biosynthesis of catecholamines. A sensitive method has been developed to assay both TH mRNA level and enzyme activity in tissue from a single rat. The time course of the induction was analysed in adrenals, locus coeruleus and substantia nigra. In both locus coeruleus and adrenals reserpine caused respectively 4.2- and 4.5-fold increase of TH mRNA which was maximal 2 days after drug injection. This increase is about twice that of the enzyme activity. No change was observed in substantia nigra. The effect lasted longer in locus coeruleus than in adrenal. In the latter, TH mRNA had almost returned to initial values at day 4 whereas at this time it is 3-fold higher in locus coeruleus and still significant at day 18. This result suggests that induction of TH results from an enhanced transcription of the TH gene. The time course difference between locus coeruleus and adrenals is most likely to result from a difference in the stability of TH mRNA in the two structures.