BIOCHEMICAL AND HISTOMORPHOMETRIC CHARACTERIZATION OF A RAT MODEL FOR HUMORAL HYPERCALCEMIA OF MALIGNANCY
BIOCHEMICAL AND HISTOMORPHOMETRIC CHARACTERIZATION OF A RAT MODEL FOR HUMORAL HYPERCALCEMIA OF MALIGNANCY
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DOI：
10.1210/endo-114-3-888
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发表时间：
1984-01-01
期刊：
影响因子：
4.8
通讯作者：
BROADUS, AE
中科院分区：
文献类型：
--
作者：
INSOGNA, KL;STEWART, AF;BROADUS, AE
恶性肿瘤引起的体液性高钙血症是一种常见但尚未完全了解的人类综合征。为了确定这种综合征的动物模型，研究了雄性Fisher大鼠中的可移植Rice-500 Leydig细胞瘤。在肿瘤移植后4-9、10-12和13-14天研究动物。到第13-14天，与对照动物相比，荷瘤动物显著高钙血症、高钙尿和高磷酸盐尿。尽管有低磷血症，但肿瘤组的磷排泄分数升高了4倍。在第13-14天，荷瘤动物的平均肾源性cAMP是对照组的5倍，而同时免疫反应性PTH [甲状旁腺激素]水平检测不到。在第14天，荷瘤动物的血浆1，25-二羟维生素DA显著升高。定量骨组织形态计量学显示肿瘤组骨细胞功能解耦，骨形成明显抑制，而骨吸收指数升高2倍以上。培养中生长的肿瘤细胞的条件培养基在胎儿骨吸收试验中始终显示出活性。这种活性是热稳定的，估计MW为30，000 - 50，000道尔顿。吲哚美辛孵育细胞对骨吸收活性没有影响。模型中的介质共享PTH的一些作用，但与天然PTH明显不同。这些发现与人类恶性体液性高钙血症的结果完全相似，唯一的例外是1，25-二羟维生素D值升高。体外骨吸收活性的证明将有助于介质的进一步表征。
Humoral hypercalcemia of malignancy is a common but incompletely understood syndrome in humans. In an effort to define an animal model of this syndrome, the transplantable Rice-500 Leydig cell tumor in male Fisher rats was studied. Animals were studied 4-9, 10-12, and 13-14 days after tumor transplanation. By days 13-14, tumor-bearing animals were significantly hypercalcemic, hypercalciuric, and hyperphosphaturic compared to control animals. Fractional phosphorus excretion was elevated 4-fold in the tumor-bearing group despite hypophosphatemia. Mean nephrogenous cAMP in the tumor-bearing animals was 5 times the value in controls at days 13-14, while simultaneous immunoreactive PTH [parathyroid hormone] levels were undetectable. Plasma 1,25-dihydroxyvitamin DA was significantly elevated in the tumor-bearing animals on day 14. Quantitative bone histomorphometry showed uncoupling of bone cell function in the tumor group, with marked suppression of bone formation while indices of bone resorption were more than 2-fold elevated. Conditioned medium from tumor cells grown in culture consistently showed activity in a fetal bone-resorbing assay. This activity was heat stable and had an estimated MW of 30,000-50,000 daltons. Incubation of cells with indomethacin had no effect on bone-resorbing activity. The mediator in the model shares some of the actions of PTH, but is clearly distinct from native PTH. The findings exactly parallel those in human humoral hypercalcemia of malignancy, with the elevated 1,25-dihydroxyvitamin D values being the sole exception. The demosntration of in vitro bone-resorbing activity will aid in further characterization of the mediator.