SEX HORMONES IN THE REGULATION OF CALCIUM HOMEOSTASIS

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中的作用 整个正常发育和怀孕期间的钙稳态 哺乳期。 为了以系统的方式探讨这个广泛的主题， 实验工作将集中在四种大鼠模型上，其中性行为 已发现怀孕和哺乳期的差异会影响 Ca 新陈代谢。 将对这些模型中的每一个进行研究，以了解性别或性别 涉及妊娠相关因素。 一旦知道并且可以 在对照实验中进行操作，将调查相关变化 存在于血液、骨骼、肾脏和肠道中。 Ca、Mg、P04 的循环水平， 甲状旁腺激素，降钙素，在适当的实验中，雌二醇， 雌三醇、黄体酮、催乳素和维生素 D 代谢物将 测量。 为了确定每个涉及的靶组织 具体案例将使用一系列技术来研究每个 参与 Ca 稳态的三个主要组织：1）骨对 PTH 将通过测量高钙反应进行体内评估 PTH注射后骨环AMP含量升高。 2） 将测量Ca、Mg、PO 4 和环AMP的尿排泄量。 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，并且 激素依赖性腺苷酸环化酶系统。 3）Ca的主动转运 外翻的肠囊将与测量结合使用 肠钙结合蛋白，并在适当的情况下评估 钙吸收分数，研究肠道钙吸收的作用 Ca 稳态中与性别相关的特定变化。 结果 这项工作将极大地扩展我们对法规的整体理解 Ca 稳态，可能有助于我们理解 绝经后骨质疏松症的发病机制。

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.