Developmental aspects of parathyroid hormone-related protein biology

Parathyroid hormone-related protein (PTHrP) has been discovered as a parathyroid hormone (PTH)-like factor responsible for the humoral hypercalcaemia of malignancies. Further studies revealed that PTHrP is ubiquitously expressed, in mature as well as in developing normal tissues from various species. Although not completely understood, the biological roles of PTHrP concern a variety of domains, including calcium phosphorus metabolism and bone mineralization, smooth muscle relaxation, cell growth and differentiation, and embryonic development. As a poly-hormone, PTHrP is now acknowledged to act via the paracrine, autocrine, and even the intracrine pathways. This review focuses on the main developmental features of the biology of PTHrP. During embryonic development, PTHrP is considered to be involved as a growth factor that promotes cell proliferation and delays cell terminal maturation. PTHrP has been shown to intervene in the development of various tissues and organs such as the skeleton, skin, hair follicles, tooth, pancreas, and the kidney. In addition, through its midregion sequence, which is able to promote an active transplacental calcium transport, PTHrP may intervene indirectly in the mineralization of the foetal skeleton. PTHrP has also been shown to be necessary for the normal development of the mammary gland, while huge amounts of PTHrP are found in the human milk. Finally, observations of physiologic, vasodilating effects of PTHrP in the kidney suggest its involvment in the control of renal hemodynamics, especially in the perinatal period.