Rizzoli R, Ferrari S L, Pizurki L, Caverzasio J, Bonjour J P
Department of Medicine, University Hospital, Geneva, Switzerland.
J Endocrinol Invest. 1992;15(9 Suppl 6):51-6.
By interacting with a structurally identical receptor, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) display a common spectrum of action on the transport of mineral elements in bone and kidney. In vivo, PTH/PTHrP similarly reduce the renal tubular reabsorption of inorganic phosphate (Pi) and increase that of calcium. The hypercalcemic effect of PTHrP is due to an increase in both bone resorption and renal calcium reabsorption, the latter through a sodium-independent mechanism. The PTHrP-stimulated bone resorption can be totally inhibited by bisphosphonate therapy. Despite that, the fall in calcemia is moderate, indicating that the PTHrP main hypercalcemic action is due to the stimulation of the renal transport of calcium. For identical effects on renal ionic transports, PTHrP appears to less stimulate bone formation than PTH. These experimental findings are similar to clinical observations in patients with primary hyperparathyroidism or with solid malignant tumors. In vitro, the effects of PTH(1-34), PTHrP(1-34) and PTHrP(1-141) on cAMP production and sodium-dependent phosphate transport (NaPiT) are similar in kidney cells, where NaPiT is specifically inhibited by either peptide. This effect is attenuated by the competitive inhibitor [D-Trp12,Tyr34]bPTH(7-34)amide. Transforming growth factor-alpha similarly modulates the cAMP and NaPiT responses to PTH/PTHrP. In cultured mammary cells isolated from lactating rats, PTHrP elicits a 2-fold increase of cAMP production. Various products of bone and stromal cells, and of leukocytes, such as Interleukin-6 or Tumor necrosis factor-alpha, as well as high extracellular calcium concentration enhance PTHrP production by cultured lung squamous cell carcinoma and Leydig tumor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
通过与结构相同的受体相互作用，甲状旁腺激素（PTH）和甲状旁腺激素相关蛋白（PTHrP）在骨骼和肾脏中矿物质元素的转运方面表现出共同的作用谱。在体内，PTH/PTHrP同样会降低肾小管对无机磷酸盐（Pi）的重吸收，并增加对钙的重吸收。PTHrP的高钙血症作用是由于骨吸收增加和肾钙重吸收增加，后者通过一种不依赖钠的机制实现。双膦酸盐治疗可完全抑制PTHrP刺激的骨吸收。尽管如此，血钙下降幅度适中，表明PTHrP主要的高钙血症作用是由于刺激了肾脏对钙的转运。对于对肾脏离子转运的相同影响，PTHrP似乎比PTH对骨形成的刺激作用更小。这些实验结果与原发性甲状旁腺功能亢进或实体恶性肿瘤患者的临床观察结果相似。在体外，PTH(1 - 34)、PTHrP(1 - 34)和PTHrP(1 - 141)对肾细胞中环磷酸腺苷（cAMP）产生和钠依赖性磷酸盐转运（NaPiT）的影响相似，在肾细胞中，任何一种肽都能特异性抑制NaPiT。这种作用会被竞争性抑制剂[D - Trp12,Tyr34]bPTH(7 - 34)酰胺减弱。转化生长因子 - α同样会调节对PTH/PTHrP的cAMP和NaPiT反应。在从泌乳大鼠分离的培养乳腺细胞中，PTHrP会使cAMP产生增加两倍。骨细胞、基质细胞和白细胞的各种产物，如白细胞介素 - 6或肿瘤坏死因子 - α，以及高细胞外钙浓度，分别会增强培养的肺鳞状细胞癌和睾丸间质细胞瘤细胞中PTHrP的产生。（摘要截选至250词）
