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Abstract

In this mini-review the role of parathyroid hormone-related peptide (PTHrP) in physiology and pathophysiology is discussed. Evolving from an unknown humoral factor in the HHM (Hypercalcemia of malignancy) syndrome its role as a "masterregulator" in the PTH family following identification is reviewed. PTHrP has more paracrine and autocrine functions in virtually all tissues than classical endocrine functions and is essential in embryonic, fetal and post-natal life. The physiological functions are near endless. The development of PTH/PTHrP receptor antagonist and agonists has been difficult and disappointing. Its role as a possible cytokine itself and as a regulatory thermogenesis factor in brown adipose tissue in cancer cachexia is discussed. PTHrP assays must be improved for PTHrP to be a reliable biomarker in oncology and to resolve the function of local proteolytic PTHrP fragments which are largely a mystery until now.