SEX HORMONES AND BODY FLUID REGULATION

性激素和体液调节

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/6638519
• 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; 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：（根据研究者的摘要进行了改编）雌激素和 孕酮在休息时和扰动期间调节体水和钠 正常的体液稳态，例如脱水，低钠血症和钠 加载中。这些效果的机制很难确定 因为雌激素和孕激素对体水和 在生殖年龄的女性中，钠调节并同时增加。在 研究设计，研究人员暂时抑制性类固醇激素 挥发性激素类似物的年轻女性的分泌物， 乙酸亮脂蛋白，然后隔离雌激素和孕酮的作用 通过添加这些激素中的每一种，在体内和钠调节上。 乙酸亮脂蛋白下调下丘脑 - 垂体 - 卵巢轴的轴 垂体水平的GNRH受体的内在化。遵循 初始刺激，长期给予乙酸亮脂抑制 类固醇基因。抑制类固醇激素后，研究人员将“添加 返回“天然雌激素和/或孕激素，为了完成 以下特定目的：1）确定雌激素对渗透的影响 精氨酸加压素的敏感性以及精氨酸的肾素敏感性 加压素。渗透刺激的精氨酸加压素（AVP）在期间增加 雌激素给药以及月经周期的阶段 雌激素和孕酮水平更高。这些协议将检查性 激素对AVP的渗透刺激和剂量反应的效果 AVP和肾脏水调节之间的关系。调查人员 假设单独雌激素并与孕酮结合 通过增加对AVP的反应来增加体内水的保留 血浆渗透压的增加。在较早的研究中，AVP在 女性性激素的升高并不总是与 人体水的保留增加，因此调查人员进一步假设 雌激素会干扰肾小管中的AVP作用。 2）确定 孕酮对肾脏钠调节的影响。孕激素的升高 引起短暂的鼻尿液，很快就被刺激抵消了 肾素 - 血管紧张素 - 醛固酮系统，以及对房屋的抑制 亚钠肽从心肌细胞释放。调查人员 假设孕酮会在钠期间增强钠的保留率 通过减轻肾素血管紧张素 - 醛固酮的抑制来加载 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 因为与保水有关的症状是80％的主要原因 女性停止激素疗法，无法利用其保护性 对心脏，骨骼和大脑的影响。