MOLECULAR BIOLOGY OF CATECHOLAMINE SYNTHESIS IN STRESS

压力在所谓疾病的发展中起着重要作用。 来自文明--心血管疾病，精神障碍， 胃肠道疾病--并促进免疫功能的发展 疾病和癌症。交感-肾上腺系统，它产生 儿茶酚胺，去甲肾上腺素和肾上腺素，是最早的系统之一 在应激状态下在生物体中被激活。 R.Kvetnansky和他的同事们早期的研究表明，慢性感冒 反复束缚应激引起血液循环显著升高。 儿茶酚胺，以及小鼠肾上腺活动的增加 儿茶酚胺生物合成酶，特别是酪氨酸羟基酶(TH) 和多巴胺β-羟基酶(DBH)。最近我们开始研究 这些酶的基因在应激状态下的表达变化。 束缚应激可显著提高TH和DBH基因的表达水平。 此外，对一个人的反应有显著的差异 对抗反复的压力。这个项目将使我们能够进一步描绘 应激条件下儿茶酚胺生物合成酶表达的变化。 具体地说，它将： 一、研究单一压力和重复压力之间的差异。例如，我们 将决定至少需要多长时间的压力才能引发 基因表达的变化，以及单个基因表达需要多少 由对第二秒的改变的反应决定的“记住”的压力 压力。 II.确定参与调控的转录因子 TH和DBH基因在单次和重复固定化过程中的表达 压力。 研究神经和体液因素的参与，特别是 神经肽对儿茶酚胺基因表达的调控 应激状态下的生物合成酶。 确定雌性SD大鼠对应激的反应是否类似于 在男性身上发现了这种反应。 这项研究的结果应该有助于对 交感-肾上腺系统激活的分子生物学基础 压力。

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.