Ostrem V K, Tanaka Y, Prahl J, DeLuca H F, Ikekawa N
Proc Natl Acad Sci U S A. 1987 May;84(9):2610-4. doi: 10.1073/pnas.84.9.2610.
1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D3, promotes the differentiation of HL-60 human promyelocytic leukemia cells into monocytes. Differentiation changes include the induction of phagocytosis, the initiation of nitroblue tetrazolium-reducing activity, and the appearance of nonspecific acid esterase. We have found that the 24-homo- and 26-homo-1,25-dihydroxyvitamin D3 and their delta 22 analogues are 10-fold more potent than 1,25-dihydroxyvitamin D3 in inducing differentiation of HL-60 cells in vitro. In vivo, these analogues show activity similar to 1,25-dihydroxyvitamin D3 in stimulating intestinal calcium transport in vitamin D-deficient rats. The 24-homoanalogues are significantly less active, whereas the 26-homo derivatives are more active than the natural hormone in mobilizing calcium from bone. This unusual activity pattern cannot be explained on the basis of the affinity of these analogues for the 1,25-dihydroxyvitamin D3 intracellular receptor: both 24-homo- and 26-homo-1,25-dihydroxyvitamin D3 have the same effectiveness as 1,25-dihydroxyvitamin D3 in displacing the tritiated hormone from its receptor in rat intestine or HL-60 cells. These analogues of 1,25-dihydroxyvitamin D3 may be of some interest as possible therapeutic substances, or as tools in understanding the action of 1,25-dihydroxyvitamin D3 in inducing differentiation.
1,25 - 二羟基维生素D3是维生素D3的激素形式，可促进HL - 60人早幼粒细胞白血病细胞分化为单核细胞。分化变化包括吞噬作用的诱导、硝基蓝四氮唑还原活性的启动以及非特异性酸性酯酶的出现。我们发现，24 - 同型和26 - 同型 - 1,25 - 二羟基维生素D3及其δ22类似物在体外诱导HL - 60细胞分化方面比1,25 - 二羟基维生素D3强10倍。在体内，这些类似物在刺激维生素D缺乏大鼠的肠道钙转运方面表现出与1,25 - 二羟基维生素D3相似的活性。24 - 同型类似物的活性明显较低，而26 - 同型衍生物在从骨骼中动员钙方面比天然激素更具活性。这种不寻常的活性模式无法基于这些类似物对1,25 - 二羟基维生素D3细胞内受体的亲和力来解释：24 - 同型和26 - 同型 - 1,25 - 二羟基维生素D3在将氚标记的激素从大鼠肠道或HL - 60细胞的受体上置换下来方面与1,25 - 二羟基维生素D3具有相同的效力。1,25 - 二羟基维生素D3的这些类似物作为可能的治疗物质或作为理解1,25 - 二羟基维生素D3诱导分化作用的工具可能会引起一些关注。
