We propose to study the molecular action of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in tissues such as intestine and kidney as well as new target organs. We plan to purify and characterize the cytoplasmic receptor protein for the 1,25(OH)2D3 hormone and investigate its influence on transcription and other aspects of RNA and protein synthesis. A second objective involves the study of the 24-hydroxylated D-vitamins, namely 24,25(OH)2D3 and 1,24,25(OH)3D3. We intend to examine the metabolic production, circulating level an potential target tissue receptors and actions of these less-well understood vitamin D sterols. Finally using radioligand binding assays in combination with high performance liquid chromatography, we will continue our research in the regulation of vitamin D metabolism in health and disease. Special emphasis will be placed on probing the physiologic control of circulating 1,25(OH)2D3. Disease states to be investigated include vitamin D resistant osteopenias, endocrine disorders and other maladies of mineral metabolism.