SEX HORMONES AND BODY FLUID REGULATION

描述：(改编自《调查者摘要》)雌激素和 黄体酮调节静息和运动时体内的水分和钠。 体液平衡正常，如脱水、低钠血症和钠 正在装车。这些影响的机制一直难以确定。 因为雌激素和黄体酮对身体水分和 在育龄妇女中钠的调节和增加是同时进行的。在……里面 研究设计，研究人员暂时抑制性类固醇激素 具有促性腺激素释放激素类似物的年轻女性的分泌， 醋酸亮丙瑞林，然后分离雌激素和黄体酮的作用 通过补充这些荷尔蒙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 促性腺激素释放激素受体在垂体水平的内化。在此之后 最初的刺激，慢性给药醋酸亮丙瑞林抑制 类固醇激素。在类固醇激素抑制后，调查人员将“增加 停用“天然雌激素和/或黄体酮”，以达到 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及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 雌激素注射以及在月经周期的各个阶段 雌激素和黄体酮水平更高。这些协议将检查性行为 AVP渗透刺激的激素效应及其量效关系 AVP与肾脏水调节的关系。调查人员 假设雌激素单独以及与黄体酮联合使用将 通过增加AVP的反应来增加整体体内的水分保持 血浆渗透压升高。在早期的研究中，AVP在 女性性激素的升高并不总是与相称的 体内水分滞留增加，因此研究人员进一步假设 雌激素干扰肾小管内AVP的作用。2)确定 孕酮对肾脏钠调节的影响。黄体酮水平升高 引起一过性钠尿，这很快就会被刺激 肾素-血管紧张素-醛固酮系统与心房抑制 心肌细胞释放利钠肽。调查人员 假设孕酮将增强钠在钠摄取过程中的滞留 减轻肾素血管紧张素-醛固酮抑制作用的负荷作用 系统和抑制ANP释放。这些研究很重要，因为它们 有助于厘清性激素对心血管系统的影响，以及 因为与水分滞留相关的症状是80% 的女性停止激素治疗并未能利用其保护性作用 对心脏、骨骼和大脑的影响。

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.