VITAMIN D RECEPTOR LEVELS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 拟议研究的目的是测试外周血单核细胞(PBM)维生素D受体水平(VDR)如何准确反映难以接触的组织中的VDR水平，特别是在肠道中。为了测试这种关系，我们建议观察低钙饮食(LCD)对PBM和十二指肠VDR的影响，并观察这两个组织中VDR水平与VDR基因表达和VDR依赖基因活性的相关性。由于测量人类靶组织中的VDR需要侵入性的活检程序，如果PBM VDR水平是其他靶组织中VDR的良好指标或替代测量，则将是有用的。因此，我们计划验证PBM VDR可以作为十二指肠粘膜受体水平的替代标记物的假设。 这一假设将通过以下三个具体目标进行检验： 1.测定正常钙摄入量和低钙饮食(LCD)状态下健康青年十二指肠粘膜VDR和PBM VDR。 2.确定LCD期间十二指肠VDR的上调是否伴随PBM VDR的类似上调。 3.通过检测VDR基因在肠粘膜和PBM中的表达以及VDR依赖的肠组织(Calbindin 9kD)和PBM(24-OHase)基因表达，评价VDR在肠粘膜和PBM中的生物学活性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of the proposed research is to test how accurately peripheral blood monocyte (PBM) vitamin D receptor level (VDR) reflects VDR levels in inaccessible tissues, specifically in the intestine. To test this relationship, we propose to observe the effect of a low calcium diet (LCD) on PBM and duodenal VDR, and to observe how well VDR levels in both tissues correlate with VDR gene expression and VDR-dependent gene activity. As measurement of VDR in human target tissues would require invasive biopsy procedures, PBM VDR levels would be useful if they were good indicators or surrogate measurements of VDR in other target tissues. Therefore, we plan to test the hypothesis that PBM VDR can serve as a surrogate marker of receptor level in duodenal mucosa. The hypothesis will be tested by the following three specific aims: 1. To measure duodenal mucosal VDR and PBM VDR in healthy young adults during normal Ca intake and during low Ca diet (LCD). 2. To determine whether duodenal VDR upregulation during LCD is accompanied by a similar upregulation of PBM VDR. 3. To estimate VDR biologic activities in intestinal mucosa and PBM by measuring VDR gene expression and gene expressions of VDR-dependent intestinal (calbindin 9kD) and PBM (24-OHase) gene expressions in each tissue.