Paracrine parathyroid hormone-related protein in bone: Physiology and pharmacology

Abstract

Parathyroid hormone-related protein (PTHrP) was discovered as the cause of cancer-related hypercalcemia but is an important paracrine/autocrine regulator in many tissues. In addition to shared actions with PTH on their common receptor, PTHR1, PTHrP has actions mediated by regions beyond the amino terminus, including promotion of placental transfer of calcium from mother to fetus and transport of PTHrP in and out of the nucleus. PTHrP generated locally is essential for normal endochondral bone formation and for bone remodeling, and full-length PTHrP is shown to be the secreted product of osteocytes. Whereas the main physiological function of PTH postnatally is the hormonal regulation of calci..