Parathyroid Hormones

This chapter focuses on the hormone produced by the parathyroid gland, parathyroid hormone (PTH), its structure, regulation, action through its known receptors, physiologic functions, and diseases. The parathyroid glands were discovered in the late 19th century and were found to be distinct from the thyroid glands and to regulate Ca2+ metabolism. The hormone was purified in 1959 and found to be an 84 amino acid peptide, which was later synthesized. Its biologic activity is contained within the first 34 amino acids. Release of PTH from the gland is regulated by extracellular Ca2+ through the calcium-sensing receptor (high inhibits, low stimulates), by phosphate (high stimulates) and by 1,25-dihydroxyvitamin D3 (negative feedback inhibition). In this manner, the hormone regulates the levels or synthesis of these three components, by action primarily on bone and kidney. It acts through its receptor, PTHR1 (a G protein–coupled receptor), in the kidney and on cells of the osteoblast lineage in bone. PTH induces the synthesis of 1,25-dihydroxyvitamin D3 by the kidney, which acts on the intestine to increase uptake of Ca2+. PTH-PTHR1 binding facilitates increased renal reabsorption of Ca2 and causes phosphaturia by downregulation of sodium/phosphate transporters. In bone, it causes many changes in gene expression through a number of signal transduction pathways in cells of the osteoblastic lineage, resulting in either catabolic or anabolic effects on bone. Because of the latter effects, PTH (1–34; teriparatide) was approved for treatment of osteoporosis. There are many diseases associated with each of these constituent parts, and these are described in the chapter. There are still gaps in our knowledge, and we have attempted to point these out.