SEX HORMONES IN THE REGULATION OF CALCIUM HOMEOSTASIS

性激素调节钙稳态

• 批准号: 3073133
• 负责人: MARY L THOMAS
• 金额: $ 5.28万
• 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/3073133
• 关键词: 25 hydroxycholecalciferol; blood; bone; calcitonin; calcium metabolism; calmodulin; cyclic AMP; estradiol; estriol; gender difference; growth /development; homeostasis; hormone regulation /control mechanism; hypercalcemia; intestines; kidney; laboratory rat; 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.

拟议研究的主要目标是获得更好的 了解女性内分泌状态在调节卵巢功能中的作用 CA在正常发育和妊娠期间的动态平衡 哺乳。为了系统地探讨这一广泛的主题， 实验工作将集中在四种大鼠模型上，在这些模型中， 已发现怀孕和哺乳的差异会影响病例 新陈代谢。这些模特中的每一个都将被研究，以了解性别-或者 与怀孕有关的因素也有涉及。一旦这一点被知道并可以 在对照实验中操纵，相关变化将被调查 在血液、骨骼、肾脏和肠道中。循环中的钙、镁、磷、磷 甲状旁腺激素，降钙素，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 量过了。为了确定每一次手术中涉及的靶组织 具体案例将使用一系列技术来研究每一个 参与钙稳态的三个主要组织：1)骨对 甲状旁腺激素将在体内通过测量高钙反应和 注射甲状旁腺素后骨环磷酸腺苷含量升高。2) 测定尿中钙、镁、磷和环磷酸腺苷的排泄量。在……里面 此外，肾皮质切片将被用来研究 25-羟基胆钙素转化为更多的极性代谢物，以及 激素依赖型腺苷环化酶系统。3)钙的主动转运 外翻的肠囊将与测量 肠道钙结合蛋白，并在适当的情况下评估 钙吸收分数，研究肠道钙吸收在其中的作用 钙稳态中与性别相关的特异性改变。结果是 这项工作将极大地扩大我们对该条例的总体认识 对钙稳态的影响，这可能有助于我们理解 绝经后骨质疏松症的发病机制。