PARATHYROID HORMONE-RELATED PROTEINS - COMING OF AGE IN THE 1990S

IN 1987, three groups announced the purification, amino acid sequencing and complimentary DNA cloning of a novel class of peptide hormones. These peptides share marked N-terminal homology with PTH (Fig. 1) and, as a result, have been variously referred to as PTH-related-protein (PTHRP), PTH-like protein, and human hypercalcemia factor. PTHRPs were purified and their cDNAs cloned from tumors associated with the syndrome of humoral hypercalcemia of malignancy (HHM), and compelling evidence suggests that in the vast majority of patients with HHM, PTHRPs are responsible for the hypercalcemia which is one of the hallmarks of the syndrome. Synthetic and recombinant PTHRPs have been documented in a number of laboratories to mimic the effects of PTH on the classical PTH target tissues, bone and kidney. Specifically, PTHRPs bind to PTH receptors and stimulate adenylate cyclase in these tissues and also stimulate osteoclastic bone resorption. © 1990 by The Endocrine Society.