Nuclear Mechanisms of the Regulation of Tyrosine HydroxylaseGene in Adrenal Medullary Cells

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A primary function of the nervous system is to help organisms adapt to external and internal conditions, by generating the appropriate adaptive response. A major cause for adaptation, in the nervous system, is due to changes in the biosynthesis of neurotransmitters, chemicals responsible for communication between nerve cells. These effects are accomplished through alterations in gene activity which are expressed specifically in neurons controlling the biosynthesis of neurotransmitters. This research project will focus on the regulation of the tyrosine hydroxylase (TH) gene, the gene responsible for the synthesis of catecholaminergic neurotransmitters. The mechanisms through which environmental and internal signals induce adaptive changes in the expression of neural genes are unknown. Previous studies conducted by the PI indicate that signals may be conveyed to the TH gene through the stimulation of two types of receptors, the acetylcholine receptor and the hormone, angiotensin II. The PI will determine whether neural and hormonal signals activate and regulate later stages of gene expression such as processing and maturation of gene products. Regions of the TH gene that are stimulated by neural and hormonal signals will be identified. This gene has been linked to many fundamental functions of the nervous system including learning, regulation, mood control and motivation. This research offers a model to explore how these functions are controlled at the molecular level.