臨床応用を目的とするビタミンD関連化合物の定量法の開発と各種細胞中での代謝に関する研究

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Vitamin D_3 is metabolized to 25-hydroxyvitamin D (25-OH-D_3) in the liver and subsequently to 1α,25-dihydroxyvitamin D (1,25(OH)_2D_3) or 24R,25-dihydroxyvitamin D_3 (24,25(OH)_2D_3) in the kidney. 1,25(OH)_2D_3, which is known as an active form of vitamin D_3, promotes calcium absorption in the small intestine and increase the resorption of calcium from bone. It is well recognized that vitamin D_2, D_3 metabolites show the same physiological activity in mammals and their plasma levels allow to distinction between endogeneous and exogeneous sources. It is now firmly established that 1,25(OH)_2D_3 has potent cell differentiating/anti-proliferative activities in addition to its role in calcemic homeostasis. This has led to search for novel vitamin D analogs with accentuated differentiating/anti-proliferative properties or calcium regulating ability. In the present review, nutritional and biochemical studies on vitamin D and its active analogs are summarized. 1. A simplified method for multiple assay of vitamin D and its metabolites in plasma was established. This method allows to determine vitamin D_2, D_3 and their metabolities evaluating nutritional and clinical status in various diseases. 2. To clarify the effects of daily administration of multivitamin preparation (200 IU/day of vitamin D_2) on vitamin D nutritional status in elderly subjects, the plasma levels of vitamin D metabolites were assayed. Although the plasma levels of 25-OH-D in elderly subjects were very low before administration, those significantly increased to the normal range by successive administration of the preparation for 4 weeks. The low levels of 1,25(OH)_2D in elderly mate increased to the normal range by the administration. High levels of PTH in elderly female decreased by the administration. These results suggest that successive daily administration of vitamin D is effective to improve the nutritional status of vitamin D in elderly subjects. 3. Active analog, 22-oxa-1,25(OH)_2D_3 (OCT) and calcipotriol (MC903), with less calcemic activity than 1,25(OH)_2D_3 bound poorly to the vitamin D binding protein (DBP). OCT and MC903 were subjected to extensive metabolism in a variety of tissues that leads to side chain truncated forms. Both analogs utilized 24-hydroxylase for inactivation in the target cells to regulate their biological activities. 4. The positive effect of 2β-3-hydroxypropoxy-1,25(OH)_2D_3 (ED-71) on prevention of bone loss in vivo was partially explained by the longer half life in blood, due to its strong binding affinity for DBP, and its low catabolic rate in target tissues.
日本ビタミン学会の論文
1998-01-25

臨床応用を目的とするビタミンD関連化合物の定量法の開発と各種細胞中での代謝に関する研究

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