GENOMIC & NONGENOMIC EFFECTS OF STEROIDS ON SALT INTAKE

基因组学

• 批准号: 6291556
• 负责人: Randall R. Sakai
• 金额: $ 22.16万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6291556
• 关键词: aldosterone; angiotensin II; appetite; behavioral /social science research tag; brain mapping; brain metabolism; corticosteroid receptors; gene environment interaction; gene expression; genetic regulation; hormone regulation /control mechanism; laboratory rat; neuropeptide receptor; nutrition related tag; salt intake

DESCRIPTION (applicant's abstract): The expression of sodium appetite in the rat is controlled by a multitude of hormonal mechanisms evoked when the animal is sodium depleted. Research has shown that it is not the sodium deficiency itself but rather the synergistic action of angiotensin and aldosterone, hormones that are released in response to the sodium depletion, which 1) generate the appetite for salt, and 2) have long-term effects that enhance subsequent salt intake. The proposed experiments examine the genomic and non-genomic effects of steroids on sodium intake and are based upon a foundation of past research examining the neurohormonal basis of sodium intake in the rat. This research proposal attempts to extend the current understanding of how and where these hormones act in the brain to elicit their specific behavioral effects by using A) site specific directed stimulation of brain parenchyma by steroids to: 1) identify those brain areas sensitive to adrenal steroids in eliciting sodium intake, and 2) to examine the mechanism by which the steroids act, i.e., either by classical genomic actions on the neurons that require hours of activation prior to eliciting a behavioral response or by acting at putative membrane receptors such that changes in behavior occur within minutes after steroid application; and B) by using current cell and molecular biological techniques in an in viva preparation to examine the effects of selective interference of endogenous steroid and peptide receptor production in brain. In addition to increasing our understanding of a classic instance of self-regulatory behavior, this research has health relevance. These results may provide rational therapies for patients in whom sodium intake complicates the management of hypertension and renal disease. With a better understanding of how endocrine mechanisms operate in eliciting sodium intake, chemical therapies that interfere with the actions of the/hormones can be directed at different levels of its production or mechanisms of action to reduce the craving for sodium.

说明(申请人的摘要)：食欲的表达 老鼠是由多种荷尔蒙机制控制的，当动物 钠已经耗尽了。研究表明，这并不是缺钠 而不是血管紧张素和醛固酮的协同作用， 钠耗竭后释放的荷尔蒙，这是1) 增加食盐的食欲，2)有长期的效果，可以增强 随后的盐分摄入量。拟议中的实验检查了基因组和 类固醇对钠摄入量的非基因组效应 过去研究钠摄入量的神经激素基础的基础 在老鼠身上。这项研究提案试图扩展目前的理解 这些荷尔蒙在大脑中如何以及在哪里起作用，从而引发它们的特异性 使用A)部位定向刺激脑的行为效应 皮质类固醇：1)识别对肾上腺敏感的大脑区域 类固醇在诱导钠摄入量中的作用，以及2)研究类固醇诱导钠摄入的机制。 类固醇的作用，也就是通过对神经元的经典基因组作用 在引发行为反应之前需要数小时的激活，或通过 作用于假定的膜受体，从而使行为发生变化 在使用类固醇后的几分钟内；以及B)通过使用当前细胞和 体内制剂中的分子生物学技术用于检测 内源性类固醇和多肽受体的选择性干预作用 大脑中的生产。 除了增加我们对一个经典实例的理解之外 自我调节行为，本研究具有健康相关性。这些结果可能 为钠摄入量并发高血压的患者提供合理的治疗方法 高血压和肾脏疾病的管理。更好地理解 内分泌机制如何在诱导钠摄入量、化学疗法中起作用 干扰/荷尔蒙的作用可以针对不同的 它的生产水平或减少渴望的行动机制 钠盐。