Parathyroid hormone (PTH) is the key hormone regulating calcium homeostasis and, as such, is an important diagnostic and prognostic marker. Although the measurement of PTH has greatly improved over the past few decades, oxidation status thereof is unaccounted for in currently used assays. PTH can be oxidized on methionine residues located at amino acid positions 8 and 18. This is a relevant post-translational modification as, due to refolding of the molecule, it results in the decreased ability to activate the PTH1 receptor. Although this loss of activity after oxidation was observed as early as 1934, only recently a method was developed to measure and distinguish non-oxidized PTH (n-oxPTH) from oxidized PTH. This method creates exciting possibilities for studying more specifically the role of n-oxPTH in physiology and pathology. Therefore, it can now be explored what the clinical implications of measuring n-oxPTH will be. Herein, we review the available evidence of the effect of oxidation on the biological activity of PTH. We also discuss studies examining the mechanism of PTH oxidation in vivo and efforts to stabilize synthetic PTH ex vivo for therapeutic applications. Lastly, the available studies regarding the clinical significance of n-oxPTH are evaluated and future directions discussed.

中文翻译：

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甲状旁腺激素的氧化。

甲状旁腺激素（PTH）是调节钙稳态的关键激素，因此，它是重要的诊断和预后标志物。尽管在过去的几十年中，PTH的测量已大大改善，但是在当前使用的测定中并没有说明其氧化状态。PTH可以在氨基酸第8和18位的蛋氨酸残基上被氧化。这是一个相关的翻译后修饰，因为由于分子的重新折叠，导致激活PTH1受体的能力降低。尽管早在1934年就观察到了氧化后这种活性的丧失，但直到最近才开发出一种方法，用于测量和区分非氧化的PTH（n-oxPTH）与氧化的PTH。该方法为更具体地研究n-oxPTH在生理学和病理学中的作用提供了令人兴奋的可能性。因此，现在可以探讨测量n-oxPTH的临床意义。在这里，我们审查氧化对PTH的生物活性的影响的可用证据。我们还将讨论检查体内PTH氧化机理以及为治疗应用而稳定体外合成PTH的研究。最后，评估了有关n-oxPTH的临床意义的可用研究，并讨论了未来的方向。