Burtis W J, Dann P, Gaich G A, Soifer N E
Divisions of Endocrinology and Metabolism, Veterans Administration Medical Center, West Haven, Connecticut 06516.
J Clin Endocrinol Metab. 1994 Feb;78(2):317-22. doi: 10.1210/jcem.78.2.8106619.
The widespread expression of the gene for PTH-related protein (PTHrP) and the high interspecies conservation of the primary sequence of even the non-PTH-like portion of the protein argue for a vital role(s) for PTHrP in normal physiology. Emerging evidence suggests that PTHrP may be processed into smaller bioactive peptides, but the circulating forms of PTHrP are not well characterized. We have measured plasma concentrations in well defined patient groups using a RIA directed toward midregion PTHrP-(37-74), compared midregion concentrations to amino-terminal and carboxy-terminal PTHrP concentrations in the same patients, and further defined the components of midregion PTHrP immunoreactivity by high pressure liquid chromatography. Patients with humoral hypercalcemia of malignancy (HHM) had concentrations of PTHrP-(37-74) immunoreactivity of 90 +/- 10 pmol/L (mean +/- SEM), 9-fold higher than PTHrP-(1-74) immunoreactivity and about 3-fold higher than PTHrP-(109-138) immunoactivity. There was no consistent elevation of midregion PTHrP in patients with local osteolytic hypercalcemia, hyperparathyroidism, or renal failure, but discrimination of these groups from HHM was less complete using PTHrP-(37-74) than using PTHrP-(1-74) immunoactivity. By reverse phase high pressure liquid chromatography, plasma PTHrP-(37-74) immunoactivity in patients with HHM was resolved into three components: 1) a major peak coeluting with that found in medium conditioned by cells transfected with human PTHrP-(1-141), which we have previously sequenced and found to represent a midregion peptide beginning at residue 38; 2) a minor peak with both PTHrP-(37-74) and -(1-74) immunoreactivity; and 3) another minor peak with PTHrP-(37-74), but not PTHrP-(1-74), immunoactivity. In conclusion, the predominant circulating form of PTHrP in patients with HHM is a midregion species similar or identical to the peptide beginning at residue 38, which has been shown to be a secretory form of PTHrP.
甲状旁腺激素相关蛋白（PTHrP）基因的广泛表达以及该蛋白非PTH样部分一级序列的高度种间保守性表明，PTHrP在正常生理过程中发挥着重要作用。新出现的证据表明，PTHrP可能被加工成更小的生物活性肽，但PTHrP的循环形式尚未得到很好的表征。我们使用针对PTHrP-(37 - 74)中部区域的放射免疫分析法（RIA）测量了明确界定的患者组中的血浆浓度，将中部区域浓度与同一患者中氨基末端和羧基末端PTHrP浓度进行了比较，并通过高压液相色谱进一步确定了中部区域PTHrP免疫反应性的成分。恶性肿瘤体液性高钙血症（HHM）患者的PTHrP-(37 - 74)免疫反应性浓度为90±10 pmol/L（平均值±标准误），比PTHrP-(1 - 74)免疫反应性高9倍，比PTHrP-(109 - 138)免疫活性高约3倍。局部溶骨性高钙血症、甲状旁腺功能亢进或肾衰竭患者的中部区域PTHrP没有持续升高，但使用PTHrP-(37 - 74)区分这些组与HHM患者不如使用PTHrP-(1 - 74)免疫反应性那么完全。通过反相高压液相色谱法，HHM患者血浆中的PTHrP-(37 - 74)免疫活性被解析为三个成分：1）一个主要峰与用人PTHrP-(1 - 141)转染的细胞培养上清液中发现的峰共洗脱，我们之前对其进行了测序，发现它代表一个从第38位残基开始的中部区域肽；2）一个同时具有PTHrP-(37 - 74)和-(1 - 74)免疫反应性的小峰；3）另一个具有PTHrP-(37 - 74)但不具有PTHrP-(1 - 74)免疫活性的小峰。总之，HHM患者中PTHrP的主要循环形式是一种中部区域的物种，与从第38位残基开始的肽相似或相同，该肽已被证明是PTHrP的一种分泌形式。
