Bonjour J P, Rizzoli R, Pizurki L, Caverzasio J
Department of Medicine, University Hospital, Geneva, Switzerland.
Prog Clin Biol Res. 1990;332:39-49.
The recently identified parathyroid hormone-related peptide (PTHrP) exerts several actions on the transport of bone mineral elements. In vitro, the effects of the synthetic amino-terminal fragment of the parathyroid hormone-related protein PTHrP (1-34) on renal cyclic AMP production, Na-dependent Pi transport and Na+/H+ exchange appear to be very similar to PTH (1-34). In vivo, in thyroparathyroidectomized rats, PTHrP reduces the tubular Pi reabsorptive capacity (TmPi/GFR) and thereby lowers the level of plasma Pi. PTHrP (1-34) brings about a dose-dependent elevation in the level of plasma Ca. The hypercalcemic effect of PTHrP (1-34) is due to both an increase in bone Ca resorption, as assessed by an increment in fasting urinary Ca, and an elevation in renal Ca reabsorption. Like PTH, the tumoral peptide does not significantly affect the overall tubular reabsorption of Na. The PTHrP-induced increase in bone Ca resorption is completely inhibitable by diphosphonate therapy. Despite this efficacious antiosteolytic response the fall in calcemia is moderate since the marked effect of PTHrP on the renal transport of Ca is maintained under diphosphonate therapy. These experimental findings are similar to clinical observations previously made with several types of solid tumors.
最近发现的甲状旁腺激素相关肽（PTHrP）对骨矿物质元素的转运有多种作用。在体外，甲状旁腺激素相关蛋白PTHrP（1-34）的合成氨基末端片段对肾环磷酸腺苷生成、钠依赖性磷转运和钠/氢交换的影响似乎与甲状旁腺激素（1-34）非常相似。在体内，在甲状腺甲状旁腺切除的大鼠中，PTHrP降低肾小管磷重吸收能力（TmPi/GFR），从而降低血浆磷水平。PTHrP（1-34）使血浆钙水平呈剂量依赖性升高。PTHrP（1-34）的高钙血症作用归因于骨钙吸收增加（通过空腹尿钙增加评估）和肾钙重吸收升高。与甲状旁腺激素一样，肿瘤肽对钠的总体肾小管重吸收没有显著影响。双膦酸盐治疗可完全抑制PTHrP诱导的骨钙吸收增加。尽管有这种有效的抗骨溶解反应，但血钙下降幅度适中，因为在双膦酸盐治疗下，PTHrP对肾钙转运的显著作用得以维持。这些实验结果与先前对几种实体瘤的临床观察结果相似。
