Yamato H, Matsumoto T, Fukumoto S, Ikeda K, Ishizuka S, Ogata E
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Endocrinology. 1989 Jan;124(1):511-7. doi: 10.1210/endo-124-1-511.
Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected [1 beta-3H]1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of [3H]24,25-(OH)2D3 to [3H]1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level. It is suggested that 24,25-(OH)2D3 plays a role in modifying serum 1,25-(OH)2D3 concentrations by affecting the metabolism of 1,25-(OH)2D3 and may have a therapeutic values in the treatment of hypercalcemia or hypercalciuria caused by 1,25-(OH)2D3 excess.
先前的研究表明，给缺钙大鼠施用24,25 - 二羟基维生素D3 [24,25-(OH)2D3]会导致显著升高的血清1,25-(OH)2D3水平呈剂量依赖性降低。尽管结果表明24,25-(OH)2D3加速了1,25-(OH)2D3的代谢，但那些实验无法确定1,25-(OH)2D3代谢增强是否在血清1,25-(OH)2D3水平降低中起作用。在本研究中，为了更具体地解决这个问题，通过微量渗透泵向维生素D缺乏的大鼠外源施用1,25-(OH)2D3来单独维持血清1,25-(OH)2D3。因此，通过测量血清1,25-(OH)2D3浓度，可以检测24,25-(OH)2D3对1,25-(OH)2D3代谢清除率（MCR）的影响。施用24,25-(OH)2D3导致1,25-(OH)2D3的MCR呈剂量依赖性增强，并且1微克/100克大鼠·天的24,25-(OH)2D3将血清24,25-(OH)2D3升高至8.6±1.3纳克/毫升，显著增加了MCR并抑制了血清1,25-(OH)2D3水平。24,25-(OH)2D3对1,25-(OH)2D3代谢的影响具有快速的时间进程，静脉注射的[1β-3H]1,25-(OH)2D3在血液中的回收率在1小时内显著降低。此外，血清水溶性部分以及尿液中的放射性增加，表明1,25-(OH)2D3迅速降解为水溶性代谢物。此外，血清1,25-(OH)2D3的降低与血清和尿钙水平的降低相关。因为在这些大鼠中[3H]24,25-(OH)2D3向[3H]1,24,25-(OH)2D3或其他代谢物的转化极少，24,25-(OH)2D3似乎未转化为其他代谢物就发挥作用。这些结果表明24,25-(OH)2D3迅速刺激1,25-(OH)2D3的代谢并降低其血清水平。提示24,25-(OH)2D3通过影响1,25-(OH)2D3的代谢在调节血清1,25-(OH)2D3浓度中起作用，并且可能在治疗由1,25-(OH)2D3过量引起的高钙血症或高钙尿症方面具有治疗价值。
