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PTHrP physiology and pathophysiology, and the PTH/PTHrP receptor 

PTHrP physiology and pathophysiology, and the PTH/PTHrP receptor
PTHrP physiology and pathophysiology, and the PTH/PTHrP receptor

David Goltzman

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date: 07 August 2020

Although PTHrP was initially discovered as the cause of hypercalcemia-associated with malignancy, this calcium modulating effect of PTHrP appears to be a minor component of its significance in physiology and pathophysiology. PTHrP is a widely expressed modulator of cell growth, differentiation, apoptosis, and differentiated function, with critical roles in skeletal growth and development, and potentially key roles in the function of many other organ systems including blood vessels, breast, and skin both in utero and in the post-natal state. The cell surface GPCR, PTH1R is critical for the function of PTHrP as a paracrine/autocrine regulator, and allows cross-over with the function of PTH, particularly when PTH is present in high circulating concentrations. Increasing evidence both in vitro and now in vivo are accumulating that demonstrates its important intracrine roles, and further studies are required to define the interaction of intracrine functions of PTHrP with its role in activating the PTH1R. Although evidence indicates that the PTH1R may be substantially reduced in multiple tissues in CKD the broad implications for dysfunction of PTHrP, as well as for PTH, and the effects of CKD on the intracrine actions of PTHrP in multiple tissues need further definition.

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