权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

SEX HORMONES AND BODY FLUID REGULATION

性激素和体液调节

基本信息

批准号：
6638519
负责人：
NINA STACHENFELD
金额：
$ 27.44万
依托单位：
JOHN B. PIERCE LABORATORY, INC.
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-05-01 至 2006-04-30
项目状态：
已结题

项目摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) Estrogen and progesterone modulate body water and sodium at rest, and during perturbations of normal body fluid homeostasis, such as dehydration, hyponatremia and sodium loading. The mechanisms for these effects have been difficult to determine because estrogen and progesterone have opposing effects on body water and sodium regulation and increase concurrently in women of reproductive age. In the research design, the investigators temporarily inhibit sex steroid hormone secretion in young women with the gondotropin releasing-hormone analog, leuprolide acetate, and then isolate the effects of estrogen and progesterone on body water and sodium regulation by adding back each of these hormones. Leuprolide acetate down-regulates the hypothalamic-pituitary-ovarian axis with internalization of the GnRH receptors at the pituitary level. Following an initial stimulation, chronic administration of leuprolide acetate suppresses steroidogenes. After steroid hormone suppression, the investigators will "add back" natural estrogen and/or progesterone, in order to accomplish the following Specific Aims: 1) To determine effects of estrogen on the osmotic sensitivity of arginine vasopressin, and renal sensitivity to arginine vasopressin. Osmotically stimulated arginine vasopressin (AVP) increases during estrogen administration and during the phases of the menstrual cycle when estrogen and progesterone levels are higher. These protocols will examine sex hormone-effects on the osmotic stimulation of AVP and the dose-response relationship between AVP and renal water regulation. The investigators hypothesize that estrogen alone and in combination with progesterone will increase overall body water retention by increasing the AVP response to increases in plasma osmolality. In earlier studies, AVP increases during elevations in female sex hormones were not always associated with commensurate body water retention increases, so the investigators further hypothesize that estrogen interferes with AVP actions in the kidney tubule. 2) To determine effects of progesterone on renal sodium regulation. Elevations in progesterone cause a transient natriuresis, which is soon counteracted by stimulation of the renin-angiotensin-aldosterone system, as well as inhibition of atrial natriuretic peptide release from cardiac myocytes. The investigators hypothesize that progesterone will enhance sodium retention during sodium loading by attenuating the inhibition of the renin angiotensin-aldosterone system and inhibiting ANP release. These studies are important because they help clarify the effects of sex hormones on the cardiovascular system, and because symptoms related to water retention are a primary reason why 80 percent of women halt hormone therapy and fail to take advantage of its protective effects on heart, bone and brain.

描述：（改编自研究者摘要）雌激素和黄体酮在休息和扰动期间调节体内水分和钠正常体液稳态，例如脱水、低钠血症和钠加载中。这些影响的机制很难确定因为雌激素和孕激素对体内水分有相反的作用钠调节与育龄妇女同时增加。在研究设计中，研究人员暂时抑制性类固醇激素年轻女性用促性腺激素释放激素类似物分泌，醋酸亮丙瑞林，然后分离雌激素和黄体酮的影响通过添加这些激素来调节体内的水分和钠。醋酸亮丙瑞林下调下丘脑-垂体-卵巢轴垂体水平 GnRH 受体的内化。继初始刺激，长期服用醋酸亮丙瑞林可抑制类固醇激素。在类固醇激素抑制后，研究人员将“添加返回”天然雌激素和/或黄体酮，以实现具体目标如下： 1) 确定雌激素对渗透压的影响精氨酸加压素的敏感性和肾脏对精氨酸的敏感性加压素。渗透压刺激的精氨酸加压素 (AVP) 在服用雌激素以及在月经周期的各个阶段雌激素和孕激素水平较高。这些协议将检查性别激素对 AVP 渗透刺激的影响和剂量反应 AVP 与肾水调节的关系。调查人员假设单独使用雌激素以及与孕激素联合使用会通过增加 AVP 反应来增加整体身体水分保留血浆渗透压增加。在早期的研究中，AVP 在女性性激素的升高并不总是与相应的相关体内水分潴留增加，因此研究人员进一步假设雌激素会干扰肾小管中 AVP 的作用。 2）确定黄体酮对肾钠调节的影响。黄体酮升高引起短暂的尿钠增多，很快就会被刺激所抵消肾素-血管紧张素-醛固酮系统，以及心房的抑制心肌细胞释放钠尿肽。调查人员假设黄体酮会增强钠潴留期间的钠潴留通过减弱肾素血管紧张素醛固酮的抑制来负荷系统并抑制 ANP 释放。这些研究很重要，因为它们帮助阐明性激素对心血管系统的影响，以及因为与保水相关的症状是 80% 的女性停止激素治疗并且未能利用其保护作用对心脏、骨骼和大脑的影响。