Parathyroid Hormone-Related Protein: Molecular Biology, Chemistry, and Actions

From observations made on patients with a high plasma calcium associated with cancer, it had long been suspected that the tumors were producing a factor with actions very similar to those of parathyroid hormone (PTH) (Albright 1941; Lafferty 1966; Mundy and Martin 1982). This issued was resolved in 1987 with the isolation and molecular cloning of a protein, PTH- related protein (PTHrP), which is most likely derived from the same ancestral gene as PTH (Moseley et al. 1987; Suva et al. 1987). Its structural similarity to PTH around the amino-terminal region is enough to bestow on it the ability to reproduce virtually all of the physiological actions of PTH. Furthermore, it can explain the biochemical similarities between certain patients with hypercalcemia in cancer and those with primary hyperparathyroidism.