Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH)/PTHrP receptor.

Parathyroid hormone-related peptide (PTHrP) has been identified as the factor responsible for the humoral hypercalcemia of malignancy (HHM). Since the cloning of the cDNA, it has become clear that PTHrP is a prohormone that is posttranslationally cleaved to yield a complex family of peptides. Through its homology to parathyroid hormone (PTH) in the amino-terminus region of the protein, it is able to bind to and activate a common PTH/PTHrP receptor. PTHrP has been shown to be a normal product of many adult and fetal tissues, where it appears to act in an autocrine/paracrine fashion to regulate organogenesis. PTHrP and the PTH/PTHrP receptor seem to be co-expressed in many tissues, but their role in the various systems is uncertain. The use of transgenic and knock-out animal models has contributed to a better understanding of the physiological role of this peptide and its receptor. In this review, the structure of their genes, their expression pattern, and some of their major physiological functions are discussed. Attention is focused on their interaction in the regulation of cartilage and bone development.