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CHANGES IN CALCIUM AND VITAMIN D METABOLISM WITH AGE

钙和维生素 D 代谢随年龄的变化

基本信息

批准号：
3152441
负责人：
HARVEY JAMES ARMBRECHT
金额：
$ 3.13万
依托单位：
SAINT LOUIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-09-01 至 1987-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152441
关键词：
1,25 dihydroxycholecalciferol aging bone metabolism bone metabolism disorder calcium metabolism cyclic AMP dietary calcium disease /disorder model gastrointestinal disorder gastrointestinal nutrient absorption normal ossification nutrition related tag parathyroid hormones pathologic bone resorption phosphorylation protein kinase vitamin metabolism

项目摘要

Many studies in humans have shown that there is a decline in the capacity of the intestine to absorb calcium (Ca) with increasing age. To study the mechanisms responsible for the decrease in Ca absorption and changes in vitamin D3 metabolism with age, we have developed the rat as an animal model. We have shown that the rat demonstrates age-related changes in Ca absorption and vitamin D3 metabolism that are very similar to those seen in humans. In addition, we have developed a new technique that uses isolated renal cortical slices to study production of 1,25-(OH)2-D3, the biologically active metabolite of vitamin D3, and its regulation in vitro in the mammal. Therefore, we propose to use this renal slice technique to answer the question "What is the mechanism responsible for the decrease in renal 1,25-(OH)2-D3 production with age?" To answer this question, we propose to test three hypotheses: a. The decreased 1,25-(OH)2-D3 production is due to a decreased responsiveness of the adult kidney to parathyroid hormone (PTH). This failure of PTH to modulate renal 1,25-(OH)2-D3 production may be due to age-related changes in one or more of the following renal components: cAMP production and degradation, cAMP-dependent protein kinase activity, and renal protein phosphorylation. b. The decreased 1,25-(OH)2-D3 production during Ca deprivation is due to decreased secretion of biologically active PTH by the adult in response to Ca deprivation. c. The decreased 1,25-(OH)2-D3 production is due to decrease production or action of growth hormone in the adult. By testing the above hypotheses in an animal model, we will determine the mechanisms responsible for the decreased 1,25-(OH)2-D production with age, which is seen in both rat and human. Knowledge of these mechanisms will suggest ways of improving 1,25-(OH)2-D production, Ca absorption, and ultimately Ca balance and bone mineralization in the elderly population.

许多对人类的研究表明，随着年龄的增长，肠道吸收钙（Ca）。研究钙吸收减少的机制和维生素D3代谢随着年龄的增长，我们已经开发了大鼠作为一种动物，模型我们已经证明，大鼠在Ca ~（2+）水平上表现出与年龄相关的变化，吸收和维生素D3代谢，非常类似于那些在人类此外，我们还开发了一种新技术，肾皮质切片研究1，25-（OH）2-D3的产生，维生素D3的生物活性代谢产物及其体外调控在哺乳动物中。因此，我们建议使用这种肾脏切片技术，回答这个问题：“什么是减少的机制，肾脏1，25-（OH）2-D3的产生与年龄的关系“为了回答这个问题，我们我想测试三个假设：A。降低的1，25-（OH）2-D3 产生是由于成年肾脏对甲状旁腺激素（PTH）。 PTH不能调节肾脏 1，25-（OH）2-D3的产生可能是由于一种或多种与年龄有关的变化，以下肾脏成分：cAMP的产生和降解， cAMP依赖性蛋白激酶活性和肾蛋白磷酸化。 B. 钙剥夺期间1，25-（OH）2-D3产生的减少是由于减少生物活性PTH的分泌由成人响应于钙剥夺。 C. 1，25-（OH）2-D3产量的下降是由于减少成人生长激素的产生或作用。通过测试在动物模型中的上述假设，我们将确定机制负责减少1，25-（OH）2-D生产随着年龄的增长，这是在老鼠和人身上都能看到。对这些机制的了解将表明提高1，25-（OH）2-D产生、钙吸收和最终钙的方法平衡和骨矿化。