Regulation of Gene Expression of Catecholamine Biosynthetic Enzymes by Stress

Abstract

Effects of repeated stress are associated with alterations in gene expression. The effect of immobilization (IMMO) stress on the expression of the genes encoding some catecholamine biosynthetic enzymes, as well as GTPcyclohydrolase I (GTPCH), the rate-limiting enzyme in the tetrahydrobiopterin biosynthetic pathway, has been recognized. This has been studied in the adrenal medulla (AM), a major source of plasma epinephrine; the sympathetic ganglia (SG), a major source of plasma norepinephrine; and the locus ceruleus (LC), the major noradrenergic nucleus in the central nervous system that modulates the response of the hypothalamus and other brain areas to stress. All of these genes have been found to be activated by IMMO. However, there are important differences in the minimal time of IMMO required for the induction of these genes and in the factors mediating the stress response. For example, 5 min of single exposure to stress is found sufficient to elicit a maximal increase in adrenal phenylethanolamine-N-methytransferase (PNMT) mRNA levels. However, to achieve maximal effect on the other genes of interest, longer times were required. The results of these studies indicate that either c-fos is not required for the induction tyrosine hydroxylase (TH) gene expression in AM or that alternative factors are involved. Studies on TH gene expression in cultured cells have identified two major promoter elements, an AP1 site and a cyclic AMP/calcium regulatory element (CRE/CaRE), each of which can independently activate TH transcription.