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

神经系统的一个主要功能是通过产生适当的适应性反应，帮助生物体适应外部和内部条件。在神经系统中，适应的一个主要原因是神经递质生物合成的变化，神经递质是负责神经细胞之间交流的化学物质。这些效应是通过改变基因活性来实现的，这些基因活性在控制神经递质生物合成的神经元中特异性地表达。这项研究项目将集中在酪氨酸羟基酶(TH)基因的调控上，该基因负责合成儿茶酚胺能神经递质。环境和内部信号诱导神经基因表达的适应性变化的机制尚不清楚。PI以前的研究表明，信号可能通过两种类型的受体(乙酰胆碱受体和激素血管紧张素II)被传递到TH基因。PI将决定神经和激素信号是否激活和调节基因表达的后期阶段，如基因产物的加工和成熟。被神经和激素信号刺激的TH基因的区域将被识别出来。这种基因与神经系统的许多基本功能有关，包括学习、调节、情绪控制和动力。这项研究提供了一个模型来探索这些功能是如何在分子水平上被控制的。

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.