SEX HORMONES AND BODY FLUID REGULATION

性激素和体液调节

• 批准号: 6390268
• 负责人: NINA STACHENFELD
• 金额: $ 27.01万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6390268
• 关键词: arginine vasopressin; body water; cardiovascular function; clinical research; electrolyte balance; estrogens; female; hormone regulation /control mechanism; human subject; hypothalamic pituitary axis; kidney function; leuprolide; osmotic pressure; pituitary gonadal axis; progesterone; renin angiotensin system; sodium ion; steroid hormone biosynthesis; women's health

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 孕酮调节身体的水和钠在休息，并在扰动 正常的体液平衡，如脱水，低钠血症和钠 加载中这些影响的机制一直难以确定 因为雌激素和孕激素对体内水分有相反的作用， 钠调节和增加同时在育龄妇女。在 研究设计，研究人员暂时抑制性类固醇激素 分泌促性腺激素释放激素类似物的年轻女性， 醋酸亮丙瑞林，然后分离雌激素和孕激素的影响 对体内水和钠的调节作用。 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。之后 醋酸亮丙瑞林的初始刺激、长期给药抑制 类固醇基因。在类固醇激素抑制后，研究人员将“添加 回”天然雌激素和/或孕激素，以实现 以下具体目的：1）确定雌激素对渗透压的影响， 精氨酸加压素敏感性和肾脏对精氨酸的敏感性 加压素渗透刺激精氨酸加压素（AVP）增加， 雌激素给药和在月经周期的阶段， 雌激素和孕激素水平更高。这些协议将检查性行为 精氨酸加压素渗透压刺激效应的剂量-效应关系 加压素与肾水调节的关系。调查人员 假设雌激素单独或与孕酮联合使用 通过增加AVP反应来增加整体身体水分保留， 血浆渗透压升高。在早期的研究中， 女性性激素的升高并不总是与相应的 身体水分潴留增加，因此研究人员进一步假设， 雌激素干扰肾小管中AVP的作用。2)以确定 孕酮对肾钠调节的影响。孕酮升高 引起短暂的尿钠排泄，这很快就被刺激 肾素-血管紧张素-醛固酮系统，以及抑制心房 从心肌细胞释放利钠肽。调查人员 假设孕酮在钠摄入期间会增强钠潴留， 通过减弱对肾素-血管紧张素-醛固酮的抑制来加载 系统和抑制ANP释放。这些研究很重要，因为它们 有助于阐明性激素对心血管系统的影响， 因为与水潴留有关的症状是80%的人 的妇女停止激素治疗，未能利用其保护性 对心脏、骨骼和大脑的影响