Induction of tyrosine hydroxylase in the locus coeruleus of transgenic mice in response to stress or nicotine treatment: lack of activation of tyrosine hydroxylase promoter activity

Abstract

Prolonged stress or chronic nicotine administration leads to induction of tyrosine hydroxylase (TH) in adrenal medulla and locus coeruleus (LC) of the rat. In this study we use mice that express a transgene encoding 4.5 kb of TH gene 5'-flanking region fused upstream of the reporter gene, human alkaline phosphatase (hAP) to test whether TH gene promoter activity is stimulated by immobilization stress, cold exposure or nicotine administration in adrenal medulla and LC. TH-hAP transgene expression is increased in response to all three stimuli in the adrenal medulla. In contrast, TH-hAP expression does not increase in response to either immobilization stress or nicotine administration in the LC and only a small induction of LC TH-hAP mRNA is observed in response to cold exposure. TH mRNA is induced 2-3 fold and TH activity is increased significantly by all three stimuli in both the adrenal and LC. These results support the hypothesis that TH expression is induced by stress or nicotine treatment in both the adrenal medulla and LC of the mouse. The induction in the adrenal is dependent primarily on transcriptional mechanisms, whereas that in the LC is apparently dependent primarily on post-transcriptional mechanisms.