[Physiological role of PTHrP]

Abstract

Parathyroid hormone related protein (PTHrP) is the aetiological factor for the syndrome of humoral hypercalcemia of malignancy. The PTHrP gene encodes three isoforms of respectively 139, 141 and 173 amino acids with N-terminal homology to parathormone (PTH). PTHrP, which has a wide tissue distribution, appears to be a polyhormone with different physiologic functions that depend on the particular fragment secreted. PTHrP may act in an autocrine, a paracrine or an endocrine fashion. There is evidence for a role in the growth and development of both embryonic and mature tissues, in cellular differentiation, in smooth muscle relaxation, lactation and calcium and magnesium transport. The best known PTHrP functions are those mediated by the N-terminal domain fixation on the classical PTH/PTHrP receptor. Nevertheless, several other functions are mediated by different fragments of PTHrP such as midregion fragments or carboxy-terminal forms. Each of these functional forms of PTHrP has one or several physiological function(s) which is (are) mediated by his own specific receptors and signal transduction pathways, some of which may be tissue specific.