The hormone, parathyroid hormone (PTH) and the paracrine factor, parathyroid hormone-related protein (PTHrP) have preserved in evolution sufficient identities in their amino-terminal domains to share equivalent actions upon a common G protein coupled receptor, PTH1R, that predominantly uses the cyclic AMP (cAMP)-protein kinase A signaling pathway. Such a relationship between a hormone and local factor poses questions about how their common receptor mediates pharmacological and physiological actions of the two. Mouse genetic studies shown that PTHrP is essential for endochondral bone lengthening in the fetus and is essential for bone remodeling. In contrast, the main postnatal function of PTH is hormonal control of calcium homeostasis, with no evidence that PTHrP contributes. Pharmacologically, amino-terminal PTH and PTHrP peptides (teriparatide and abaloparatide) promote bone formation when administered by intermittent (daily) injection. This anabolic effect is remodeling-based with a lesser contribution from modeling. The apparent lesser potency of PTHrP than PTH peptides as skeletal anabolic agents could be explained by lesser bioavailability to PTH1R. By contrast, prolongation of PTH1R stimulation by excessive dosing or infusion, converts the response to a predominantly resorptive one by stimulating osteoclast formation. Physiologically, locally generated PTHrP is better equipped than the circulating hormone to regulate bone remodeling, which occurs asynchronously at widely distributed sites throughout the skeleton where it is needed to replace old or damaged bone. While it remains possible that PTH, circulating within a narrow concentration range, could contribute in some way to remodeling and modeling, its main physiological role is in regulating calcium homeostasis.

中文翻译：

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使用它们的共享受体PTH1R，PTH和PTHrP在骨骼中的生理和药理作用。

激素，甲状旁腺激素（PTH）和旁分泌因子，甲状旁腺激素相关蛋白（PTHrP）在进化过程中保留了氨基末端结构域中的足够身份，可共同作用于共同使用的G蛋白偶联受体PTH1R环AMP（cAMP）-蛋白激酶A信号通路。激素和局部因子之间的这种关系提出了一个问题，即它们的共同受体如何介导两者的药理和生理作用。小鼠遗传学研究表明，PTHrP对于延长胎儿的软骨内骨骼至关重要，对于骨骼重塑也必不可少。相反，PTH的主要产后功能是激素对钙稳态的控制，没有证据表明PTHrP起作用。在药理上 当通过间歇（每日）注射给药时，氨基末端的PTH和PTHrP肽（teriparatide和abaloparatide）可促进骨形成。这种合成代谢作用是基于重构的，而建模的贡献较小。与PTH肽相比，PTHrP作为骨骼合成代谢药物的效力明显较低，这可以通过对PTH1R的较低生物利用度来解释。相比之下，通过过量给药或输注延长PTH1R刺激，可通过刺激破骨细胞形成将反应转化为主要吸收性反应。从生理上讲，本地产生的PTHrP比循环荷尔蒙更好地调节骨骼重塑，骨骼重塑是异步发生在整个骨骼广泛分布的部位，需要替换旧的或受损的骨骼。虽然PTH仍然有可能，