1Alpha-hydroxyvitamin D3. An analog of vitamin D which apparently acts by metabolism to 1alpha, 25-dihydroxyvitamin D3.
1Alpha-hydroxyvitamin D3. An analog of vitamin D which apparently acts by metabolism to 1alpha, 25-dihydroxyvitamin D3.
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1α-羟基维生素D3。
DOI：
10.1021/bi00717a006
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发表时间：
1974
期刊：
影响因子：
2.9
通讯作者：
M. Haussler
中科院分区：
文献类型：
--
作者：
J. Zerwekh;P. Brumbaugh;D. Haussler;Douglas J. Cork;M. Haussler
羟基维生素 D3 (la-OH-D3) 是一种合成甾醇，其生物学特性与 1a, 25-二羟基维生素 D3 (la, 25-(OH) 2-D3)（维生素 D 的表观激素形式）的生物学特性相似。合成甾醇在体内实际上与天然激素等效，最近已用于治疗维生素 D 代谢缺陷的患者。然而，目前尚无关于其生化作用模式的信息。为了确定 ifla-OH-D3 通过直接结合 1a, 25-(OH) 2-D3 的靶组织受体或首先代谢为 1a, 25-(OH) 2-D3 的功能，我们对两种甾醇的比较生物学效应以及受体结合特性进行了详细检查。单次口服 162.5 pmol（2.5 IU）la-OH-D3 或 la, 25-(OH) 2-D3 后，佝偻病雏鸡肠道钙吸收量相应增加；经过 2-3 小时的潜伏期后，两种甾醇在 9 小时时产生最大效应，并且反应在 24 小时至 72 小时之间经历平行衰减。比较 9 小时时刺激钙吸收所需的 1a-OH-D3 和 1a, 25-(OH) 2-D3 的相对量表明甾醇在 19.5-650pmol (0.3-10 IU) 的剂量范围内是等价的。在长期给药研究中，合成甾醇的抗佝偻病作用略强于
Hydroxyvitamin D3 (la-OH-D3) is a synthetic sterol with biological characteristics similar to those of la, 25-dihydroxyvitamin D3 (la, 25-(OH) 2-D3), the apparent hormonal form of vitamin D. The synthetic sterol is virtually equipotent to the natural hormone, in vivo, and has been utilized recently to treat patients with defects in vitamin D metabolism. However, no information is presently available on its biochemi-cal mode of action. In order to determine ifla-OH-D3 functions by binding directly to target tissue receptors for la, 25-(OH) 2-D3 or is first metabolized to la, 25-(OH) 2-D3, we have carried out a detailed examination of the comparative biologic effects as well as the receptor binding properties of the two sterols. After a single oral dose of 162.5 pmol (2.5 IU) of either la-OH-D3 or la, 25-(OH) 2-D3, rachitic chicks display equivalent increases in calcium absorption from the intestine; following a 2-3-hr latentperiod, both sterols elicit maximal effects at 9 hr and the responses undergo parallel decay between 24 and 72 hr. Comparison of the relative amounts of la-OH-D3 and la, 25-(OH) 2-D3 required to stimulate calcium absorption at 9 hr indicates that the sterols are equipotent in the dose range of 19.5-650pmol (0.3-10 IU). In chronic administration studies, the synthetic sterol was slightly more antirachitic than