SEX HORMONES IN THE REGULATION OF CALCIUM HOMEOSTASIS

性激素调节钙稳态

• 批准号: 3073132
• 负责人: MARY L THOMAS
• 金额: $ 5.32万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3073132
• 关键词: 25 hydroxycholecalciferol; blood; bone; calcitonin; calcium metabolism; cyclic AMP; estradiol; estriol; gender difference; growth /development; homeostasis; hormone regulation /control mechanism; hypercalcemia; intestines; kidney; lactation; magnesium; nutrition related tag; osteoporosis; parathyroid hormones; phosphates; postmenopause; pregnancy; progesterone; prolactin; sex hormones; vitamin metabolism

The major objective of the proposed research is to gain a better understanding of the role of female endocrine status in the regulation of Ca homeostasis throughout normal development and during pregnancy and lactation. In order to approach this broad topic in a systematic fashion, the experimental work will focus on four rat models in which sex differences or pregnancy and lactation have been found to affect Ca metabolism. Each of these models will be studied to learn what sex- or pregnancy-related factors are involved. Once this is known and can be manipulated in controlled experiments, related changes will be investigated in blood, bone, kidney and intestine. Circulating levels of Ca, Mg, P04, parathyroid hormones, calcitonin and in appropriate experiments, estradiol, estriol, progesterone, prolactin and vitamin D metabolites will be measured. In order to determine the target tissues involved in each of the specific cases a series of techniques will be used to study each of the three major tissues involved in Ca homeostasis: 1) bone responsiveness to PTH will be evaluated in vivo by measuring the hypercalcemic response and the elevation in bone cyclic AMP content following PTH injection. 2) Urinary excretion of Ca, Mg, P04, and cyclic AMP will be measured. In addition, renal cortical slices will be used to study conversion of 25-hydroxycholecalcificol to more polar metabolites, and the hormone-dependent adenylate cyclase system. 3) Active transport of Ca by everted gut sacs will be used in conjunction with measurements of intestinal calcium-binding protein, and in appropriate cases evaluation of fractional Ca absorption, to study the role of intestinal Ca absorption in the specific sex-related alterations in Ca homeostasis. The results of this work will greatly expand our overall understanding of the regulation of Ca homeostasis and may contribute significantly to our understanding of the pathogenesis of postmenopausal osteoporosis.

本研究的主要目的是获得一个更好的 了解女性内分泌状态在调节 在整个正常发育和怀孕期间的钙稳态， 哺乳期 为了系统地探讨这一广泛的专题， 实验工作将集中在四种大鼠模型上， 怀孕和哺乳期的差异会影响Ca 新陈代谢. 每一个模型都将被研究，以了解什么样的性别-或 与怀孕有关的因素。 一旦知道了这一点， 在对照实验中操作，将研究相关变化 在血液、骨骼、肾脏和肠道中。 循环中的Ca、Mg、P04， 甲状旁腺激素、降钙素和在适当的实验中，雌二醇， 雌三醇、孕酮、催乳素和维生素D代谢物将 测定了 为了确定每种肿瘤中涉及的靶组织， 具体情况下，一系列的技术将被用来研究每一个 三种主要组织参与Ca稳态：1）骨对 将通过测量高钙血症反应在体内评价PTH， 注射PTH后骨环AMP含量升高。 （二） 将测量Ca、Mg、PO 4和环AMP的尿排泄。 在 此外，肾皮质切片将用于研究 25-羟基胆钙化醇转化为极性更强的代谢物， 依赖腺苷酸环化酶系统。 3)钙的主动转运 外翻肠囊将与以下测量结合使用： 肠钙结合蛋白，并在适当的情况下评估 钙吸收分数，研究肠道钙吸收在 钙稳态的特定性别相关改变。 的结果 这项工作将大大扩展我们对该法规的整体理解 钙稳态，并可能有助于我们了解显着 绝经后骨质疏松症的发病机制。