This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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