1,25-DIHYDROXYVITAMIN D FUNCTION AND RECEPTOR OCCUPANCY

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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.