Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium:: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays
Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium:: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays
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DOI：
10.1210/jc.2005-1628
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发表时间：
2006-01-01
影响因子：
5.8
通讯作者：
Cantor, T
中科院分区：
文献类型：
--
作者：
D'Amour, P;Räkel, A;Cantor, T
背景：HPLC 分离后通过 PTH 测定揭示的循环 PTH 峰的定量评估构成了研究 PTH 分子形式行为的最佳方法，但也是不切实际的。目的：本研究的目的是通过使用循环 PTH HPLC 分离前后不同特异性的 PTH 测定得出的 PTH 片段/PTH (1-84) 比率，研究钙对循环 PTH 分子形式的调节。设计：CaCl2 和柠檬酸钠注入八名志愿者。在与 PTH 结构的区域 1-2 (CA)、12-18 (T) 和 65-69 (C) 反应的 PTH 测定中，测量血清和 HPLC 组分中不同钙浓度的 PTH。 结果：从低钙血症到高钙血症，C/CA 比值具有最高范围（1.92 至 9.75；P < 0.001），并且 C/T 比值具有更高范围（1.69 至6.11；P < 0.01）高于 T/CA 比率（1.15 至 1.86）。在低钙血症和高钙血症 HPLC 分析中，人 (h) PTH (1-84) 分别占循环 PTH 的 32.7% 和 4.3%。对于氨基末端 (N)-PTH（与 hPTH (1-84) 不同的 PTH 氨基末端形式），这些数字分别为 5% 和 0.9%；对于非 (1-84) PTH 或具有部分保留 N 结构的大 C-PTH 片段，这些数字为 7.3% 和 6.8%；对于缺少 N 结构的 C-PTH 片段，这些数字为 54.9% 和 88.1%。 HPLC C-PTH 片段与 hPTH (1-84) 的比率具有最广泛的范围（1.67 至 20.58）。尽管存在定量差异，但所有比率都鉴定出 PTH 片段相对于 PTH (1-84) 的相同行为。结论：PTH 测定比率是研究 PTH 分子形式调节的充分工具，即使所有 PTH 测定都显示与某些循环形式的 PTH 存在一些不良交叉反应。
Context: The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical.Objective: The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH.Design: CaCl2 and Na citrate were infused in eight volunteers. PTH was measured in serum and HPLC fractions at different calcium concentrations in PTH assays reacting with regions 1-2 (CA), 12-18 (T), and 65-69 (C) of the PTH structure.Results: From hypo- to hypercalcemia, the C/CA ratio had the highest range (1.92 to 9.75; P < 0.001), and the C/T ratio had a higher range (1.69 to 6.11; P < 0.01) than the T/CA ratio (1.15 to 1.86). Human (h) PTH (1-84) represented 32.7 and 4.3% of circulating PTH in hypo- and hypercalcemic HPLC profiles, respectively. These numbers were 5 and 0.9% for amino-terminal (N)-PTH, an amino-terminal form of PTH distinct from hPTH (1-84), 7.3 and 6.8% for non-(1-84) PTH or large C-PTH fragments with a partially preserved N structure, and 54.9 and 88.1% for C-PTH fragments missing a N structure. The HPLC C-PTH fragments to hPTH (1-84) ratio had the most extensive range (1.67 to 20.58). Despite their quantitative differences, all ratios identified identical behavior of PTH fragments relative to PTH (1-84).Conclusions: PTH assay ratios are an adequate tool to investigate the modulation of PTH molecular forms, even if all PTH assays show some undesirable cross-reactivity with certain circulating forms of PTH.