Publisher Summary This chapter focuses on parathyroid hormone (PTH), which is believed to increase serum calcium, partly by increasing the rate of bone remodeling. The physiological action of PTH is to maintain the ambient concentration of ionized calcium in blood by influencing calcium reabsorption from the glomerular filtrate of kidney tubule cells and indirectly by enhancing calcium absorption from the gut through increased activity of renal vitamin D-l-hydroxylase, which produces l α,25(OH)2D3. PTH also initiates a series of events, which result in release of skeletal calcium by osteoclasts. There is strong evidence that PTH stimulates both the insulin-like growth factor (IGF) and transforming growth factor-β (TGF-β) systems in osteoblasts. The insulin-like growth factor regulatory system is composed of two growth factors (IGF-I and IGF-II), two receptors, six binding proteins which regulate IGF bioavailability, and IGF-binding protein (IG-FBP)-specific proteases. After PTH binding to the osteoblast PTH receptor and the generation of cAME, these cells produce more IGF-II, IGFBPs -1, -4, and -5, and the IGFBP-3 and -5 proteases. PTH also directly stimulates the synthesis of TGF-β by mature osteoblasts. IGF-I, IGF-II, and TGF-β secreted by osteoblasts can be bound to the collagen matrix of bone where they reside as a sort of growth factor bank. When PTH induces osteoclastic bone resorption during the bone remodeling cycle, growth factors are released into the immediate environment where they can act on resident osteoblasts. The anabolic effect of PTH also results in the appearance of multistacked active osteoblasts at sites of bone formation.