Publications

Many physiologic roles of PTHrP are emerging. The protein functions locally in diverse tissues, often regulating the entry of cells into a differentiation pathway or acting as an epithelial signal in epithelial-mesenchymal interactions. To carry out these functions, PTHrP uses the receptor it shares with PTH or one of several PTHrP receptors that have evolved to recognize selectively the PTH-like region of PTHrP or other domains. Thus, PTHrP is a polyhormone. An exquisite selectivity barrier allows PTHrP to carry out its local tissue functions at the same time PTH uses their shared receptor to regulate systemic calcium homeostasis. This barrier is breached under pathologic circumstances, such as when malignant tumors secrete enough PTHrP into blood to cause PTH-like effects, including hypercalcemia. Powerful genetic models that have been developed in the past 7 years promise to give continuing insights into the physiology and pathophysiology of PTHrP.

Medical therapy is useful in cases of acute primary hyperparathyroidism, patients with recurrent disease, and parathyroid carcinoma. Among the therapeutic agents that have been employed, oral phosphate, bisphosphonates, and estrogens have been successful. The newly described calcimimetic agents directly block secretion of parathyroid hormone from the glands and offer an important new approach to medical therapy of primary hyperparathyroidism.