PTH (parathyroid hormone) is a critical hormone in the regulation of Ca++ homeostasis. PTH is secreted by the chief cells of the parathyroid glands as a polypeptide. PTH secretion is enhanced by low Ca++ concentrations and inhibited by FGF-23. In normal human plasma, PTH correlates negatively with active Vitamin D and positively with ionized calcium. Human and other mammalian PTH will bind and stimulate human or rat PTH1R, activating adenylate cyclase and increasing cAMP production. PTH promotes secretion of TRANCE/RANKL and periostin through PTH1R binding on osteoblasts and/or bone marrow stromal cells TRANCE/RANKL induces differentiation of osteoclasts, which in turn promote release of Ca++ from bone. PTH1R on osteocytes, however, allows PTH to promote bone formation and IGF-1 production. In addition, PTH increases hematopoietic stem cell proliferation and mobilization and induces arterial vasodilation by regulating Ca++ influx in PTH1R-expressing arterial smooth muscle. In renal epithelium, PTH promotes conversion of Vitamin D to its active form, lowers Ca++ excretion and increases phosphate excretion.