MOLECULAR BIOLOGY OF CATECHOLAMINE SYNTHESIS IN STRESS

压力在所谓疾病的发展中起着重要作用 心血管疾病，精神疾病， 胃肠道疾病-并促进免疫系统的发展 疾病和癌症。 交感肾上腺系统，产生 儿茶酚胺，去甲肾上腺素和肾上腺素，是最早的系统之一， 在压力下被激活。 R. Kvetnansky和同事的研究表明， 反复的制动应激引起循环中的 儿茶酚胺，以及肾上腺活动的增加， 儿茶酚胺生物合成酶，特别是酪氨酸羟化酶（TH） 和多巴胺β-羟化酶（DBH）。 最近我们开始研究 这些酶的基因表达随着压力的变化。 束缚胁迫显著提高TH和DBH mRNA水平。 此外，对一个单一的 与反复的压力相比。 该项目将使我们能够进一步描绘 应激条件下儿茶酚胺类生物合成酶表达的变化。 具体而言，它将： 研究单一压力和重复压力之间的差异。 比如我们 将决定什么是最小的压力所需的时间， 基因表达的变化，以及单个细胞需要多少， 被“记住”的压力，取决于对第二个 应力 II.确定参与调节转录因子， TH和DBH基因在单次和重复固定期间的表达 应力 III.研究神经和体液因素的参与，特别是 神经肽，在调节基因表达的儿茶酚胺 生物合成酶在逆境中的作用 IV.确定雌性Sprague道利大鼠对应激的反应是否类似于 在男性中发现的反应。 这项研究的结果应有助于对 交感肾上腺系统激活的分子生物学基础 应力

Stress plays a significant role in the development of so called diseases from civilization -- cardiovascular diseases, mental disorders, gastrointestinal disorders -- and facilitates the development of immune diseases and cancer. The sympathoadrenal system, which produces the catecholamines, norepinephrine and epinephrine, is one of the first systems activated in an organism during stress. Earlier studies by R. Kvetnansky and coworkers, showed that chronic cold and repeated immobilization stress elicited a large rise in circulating catecholamines, as well as an increase in adrenal activities of the catecholamine biosynthetic enzymes, particularly tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). Recently we have begun to study changes in expression of the genes for these enzymes with stress. Immobilization stress was found to markedly elevate TH and DBH mRNA levels. Moreover, there was a striking difference in the response to a single versus repeated stress. This project will enable us to further delineate the changes in expression of catecholamine biosynthetic enzymes in stress. Specifically it will: I.Study differences between a single and repeated stress. For example, we will determine what is the minimum time of stress required to elicit changes in gene expression, as well as how much is required for the single stress to be "remembered" as determined by an altered response to a second stress. II.Ascertain the transcription factors involved in regulation of the expression of TH and DBH genes during a single and repeated immobilization stress. III.Study the involvement of neural and humoral factors, and specifically neuropeptides, in the regulation of gene expression of catecholamine biosynthetic enzymes in stress. IV.Ascertain if female Sprague Dawley rats respond to stress similarly to the response found in males. The results of this study should contribute to a new understanding of the molecular biological basis of activation of the sympathoadrenal system in stress.