Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale School of Medicine, TAC S131, Box 208020, New Haven, Connecticut 06520-8020, USA.
J Clin Endocrinol Metab. 2012 Sep;97(9):2947-56. doi: 10.1210/jc.2012-2142. Epub 2012 Jun 28.
PTHrP was identified as a cause of hypercalcemia in cancer patients 25 yr ago. In the intervening years, we have learned that PTHrP and PTH are encoded by related genes that are part of a larger "PTH gene family." This evolutionary relationship permits them to bind to the same type 1 PTH/PTHrP receptor, which explains why humoral hypercalcemia of malignancy resembles hyperparathyroidism. This review will outline basic facts about PTHrP biology and its normal physiological functions, with an emphasis on new findings of the past 5-10 yr. The medical and research communities first became aware of PTHrP because of its involvement in a common paraneoplastic syndrome. Now, research into the basic biology of PTHrP has suggested previously unrecognized connections to a variety of disease states such as osteoporosis, osteoarthritis, and breast cancer and has highlighted how PTHrP itself might be used in therapy for osteoporosis and diabetes. Therefore, the story of this remarkable protein is a paradigm for translational research, having gone from bedside to bench and now back to bedside.
甲状旁腺激素相关蛋白（PTHrP）在 25 年前被确定为癌症患者高钙血症的病因。在这期间，我们了解到 PTHrP 和 PTH 是由相关基因编码的，这些基因是更大的“甲状旁腺素基因家族”的一部分。这种进化关系使它们能够与相同的类型 1 甲状旁腺素/甲状旁腺素相关蛋白受体结合，这解释了为什么恶性肿瘤引起的体液性高钙血症类似于甲状旁腺功能亢进症。这篇综述将概述 PTHrP 生物学及其正常生理功能的基本事实，重点介绍过去 5-10 年的新发现。医学和研究界最初是因为 PTHrP 参与了一种常见的副肿瘤综合征而意识到它的存在。现在，对 PTHrP 基础生物学的研究表明，它与多种疾病状态（如骨质疏松症、骨关节炎和乳腺癌）之间存在以前未被认识到的联系，并强调了 PTHrP 本身如何用于治疗骨质疏松症和糖尿病。因此，这种非凡蛋白质的故事是转化研究的典范，它已经从床边走向了实验室，现在又回到了床边。
