CREM and ICER are differentially implicated in trans-synaptic induction oftyrosine hydroxylase gene expression in adrenal medulla and sympathetic ganglia of rat

Reserpine treatment leads to a trans-synaptic increase of the tyrosine hydr oxylase (TH) gene transcription rate, mRNA and protein levels in catecholam inergic tissues including the adrenal medulla (AM) and the superior cervica l ganglia (SCG), The TPA-responsive element plays an important role in the trans-synaptically-induced transcription of the TH gene in the AM, whereas it does not appear to be involved in the SCG (Trocme et al. [1997] J, Neuro sci. Res. 48:489-498). In this study, we show that another regulatory seque nce of the TH proximal promoter, the cAMP-responsive element (CRE), binds d ifferent factors in the AM and in the SCG, To elucidate the dynamics of pro moter regulation a complete time course analysis was conducted. Reserpine t reatment enhances, between 1 hr and 8 hr after the injection, the expressio n and the binding of the repressor ICER in the AM, whereas in the SCG it en hances the binding of CREM factors. These results suggest that the mechanis ms mediating trans-synaptic induction of the TH gene are different in the A M and SCG, The interplay between positive and negative transcription factor s and their kinetics of action are responsive of the long-term regulation o f the TH gene. (C) 2001 Wiley-Liss, Inc.