1,25-DIHYDROXYVITAMIN D FUNCTION AND RECEPTOR OCCUPANCY

这些研究将针对：(A)扩大对被占领地区的研究 1，25-二羟基维生素D3(1，25(OH)2D3)受体对大鼠的作用 用于内分泌研究的主要哺乳动物模型，以及(B)测试 假设出人意料的广泛分布的组织分布 1，25(OH)2D3受体反映了迄今为止未被认识到的作用 维生素D内分泌系统调节细胞内钙功能。 这一系列研究的方法将是使用一种特别的 灵敏的蔗糖梯度受体检测技术寻找1，25(OH)2D3 一系列组织中的受体，其中钙已知具有 专业角色(S)。那么这些受体的功能将是 通过确定受体是否被占用来评估 生理条件和检查特定终点的组织 1，25(OH)2D3的作用-维生素D诱导的钙结合蛋白 (CABP)。为了分析被占领的受体位置，我们将开发一种 最近报道的交换试验的修改版本 鸡肠道1，25(OH)2D3受体的测定 粘膜。交换法定量测定1，25(OH)2D3 大鼠的受体也将被应用于研究，以确定 不同条件下受体占有率和总受体水平的动态变化 大鼠的生理状态，并将其模式与 之前在《雏鸟》中描述过。这些相互关联的研究 1，25(OH)2D3受体的功能将大大增加我们对 维生素D内分泌系统，将为未来的评估提供基础 1，25(OH)2D3的功能在正常人和疾病患者中都有作用。

These studies will be directed toward (a) extending studies of occupied 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) receptor function to the rat, a major mammalian model for endocrine research, and (b) testing the hypothesis that the unexpectedly widespread tissue distribution of 1,25(OH)2D3 receptors reflects a heretofore unrecognized role for the vitamin D endocrine system in regulating intracellular calcium functions. The approach to this series of studies will be to use a particularly sensitive sucrose gradient receptor detection technique to seek 1,25(OH)2D3 receptors in a series of tissues where calcium is known to have a specialized role(s). Then the functionality of these receptors will be assessed by determining whether the receptors are occupied under physiological conditions and examining the tissues for a specific endpoint of 1,25(OH)2D3 action - the vitamin D induced calcium binding protein (CaBP). In order to analyze the occupied receptor sites we will develop a modified version of the exchange assay recently reported for the measurement of occupied 1,25(OH)2D3 receptors in the chick intestinal mucosa. The exchange assay for quantitation of occupied 1,25(OH)2D3 receptors in the rat will also be applied in studies to establish the dynamics of receptor occupancy and total receptor levels under a variety of physiological states in the rat and to compare their patterns to those previously described in the chick. These interrelated studies of 1,25(OH)2D3 receptor function will add much to our understanding of the vitamin D endocrine system and will provide a basis for future assessments of 1,25(OH)2D3 function in both normal and diseased individuals.