Physiological and Pharmacological Roles of PTH and PTHrP in Bone using their Shared Receptor, PTH1R.

Physiological and Pharmacological Roles of PTH and PTHrP in Bone using their Shared Receptor, PTH1R. Endocr Rev. 2021 Feb 10;: Authors: Martin TJ, Sims NA, Seeman E Abstract 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 pre...
Source: Endocrine Reviews - Category: Endocrinology Tags: Endocr Rev Source Type: research