Parathyroid hormone (PTH), which is also designated parathyrin, is an 84 amino acid single chain peptide that functions to regulate calcium metabolism by raising blood calcium through various mechanisms. PTH stimulates bone formation to increase bone mass and strength in rats and humans. Within the PTH molecule, the essential activity is associated with the first 34 amino acids at the amino-terminus of the molecule. The gene encoding PTH maps to human chromosome 11p15.3-p15.1. Parathyroid hormone-related protein (PTH-rP) is an autocrine factor that is structurally related to PTH yet, unlike PTH, which is synthesized only by the parathyroid cells, PTH-rP is synthesized by several cell types. PTH-rP regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Isolated from the culture medium of a human lung cancer cell line, PTH-rP produces PTH-like effects that are characterized as humoral hypercalcemia of malignancy. PTH and PTH-rP are both regulated by vitamin D and steroid hormones and preferentially bind to specific PTH/PTH-rP receptors, then activate adenylate cyclase or PLC (beta) via PKC activation.