GENOMIC & NONGENOMIC EFFECTS OF STEROIDS ON SALT INTAKE

描述（申请人摘要）： 大鼠是由多种激素机制引起的，当动物 是钠耗尽的研究表明，这不是钠缺乏症 而是血管紧张素和醛固酮的协同作用， 响应钠消耗而释放的激素，1） 产生对盐的食欲，2）具有增强 随后的盐摄入量。拟议的实验检查基因组和 类固醇对钠摄入量的非基因组效应，并基于 过去研究的基础，检查钠摄入的神经激素基础 在老鼠。这项研究建议试图扩展目前的理解 这些激素在大脑中的作用方式和位置， 通过使用A）脑的部位特异性定向刺激的行为效应 通过类固醇来观察脑实质：1）识别对肾上腺皮质敏感的脑区 类固醇在诱发钠摄入，和2）检查的机制， 类固醇的作用，即，要么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， 作用于假定的膜受体，使得行为发生变化 B）通过使用当前细胞， 分子生物学技术在体内制备，以检查 内源性类固醇和肽受体的选择性干扰作用 脑内生产。 除了增加我们对一个典型的 自我调节行为，这项研究具有健康相关性。这些结果可能 为钠摄入量增加的患者提供合理的治疗， 高血压和肾脏疾病的管理。更好地了解 内分泌机制如何引起钠摄入，化学疗法 干扰激素作用的药物可以针对不同的 其生产水平或行动机制，以减少对 钠。

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.