Scharla S H, Minne H W, Oswald C, Lempert U G, Schmidt-Gayk H, Ziegler R
Department of Internal Medicine 1 (Endocrinology and Metabolism), University of Heidelberg, FRG.
Bone Miner. 1989 May;6(2):155-64. doi: 10.1016/0169-6009(89)90047-0.
We have studied vitamin D metabolism in rats with the transplantable hypercalcemic Walker carcinosarcoma 256, which is a well characterized animal model for humoral hypercalcemia of malignancy. 25-Hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations were determined in blood samples obtained from parathyroidectomized (PTX) female rats at different time intervals after intramuscular tumor cell inoculation. We observed a dramatic increase in serum 1,25(OH)2D3 (280 +/- 184 vs. 98 +/- 31 pmol/l) 6 days after tumor cell injection and 4 days after the initial rise of serum calcium, whereas 25(OH)D3 tended to decrease. In a separate control experiment we compared this to the effect of exogenous parathyroid hormone in PTX rats and found similar results. In contrast, rats exhibited no change in vitamin D metabolite blood concentration after inoculation of the normocalcemic Yoshida sarcoma, which obviously does not interfere with vitamin D metabolism. We conclude that the humoral bone-resorbing agent produced by the Walker tumor cells causes elevation of serum 1,25(OH)2D3 concentration by this fulfilling an additional criterion of PTH-like activity.
我们研究了移植性高钙血症沃克癌肉瘤256大鼠的维生素D代谢情况,该模型是恶性肿瘤体液性高钙血症的典型动物模型。在肌肉注射肿瘤细胞后的不同时间间隔,从甲状旁腺切除(PTX)的雌性大鼠采集血样,测定其中25-羟基维生素D3(25(OH)D3)和1,25-二羟基维生素D3(1,25(OH)2D3)的浓度。我们观察到,在肿瘤细胞注射6天后以及血清钙开始升高4天后,血清1,25(OH)2D3显著升高(从98±31 pmol/L升至280±184 pmol/L),而25(OH)D3则呈下降趋势。在另一项对照实验中,我们将此结果与PTX大鼠注射外源性甲状旁腺激素的效果进行比较,得到了相似的结果。相比之下,接种血钙正常的吉田肉瘤的大鼠,其血液中维生素D代谢产物浓度没有变化,显然吉田肉瘤不会干扰维生素D代谢。我们得出结论,沃克肿瘤细胞产生的体液性骨吸收剂可使血清1,25(OH)2D3浓度升高,从而满足了类似甲状旁腺激素活性的另一标准。