Parathyroid hormone

1BWX, 1ET1, 1FVY, 1HPH, 1HPY, 1HTH, 1ZWA, 1ZWB, 1ZWD, 1ZWE, 1ZWF, 1ZWG, 2L1X, 3C4M574119226ENSG00000152266ENSMUSG00000059077P01270Q9Z0L6NM_000315NM_001316352NM_020623NP_000306NP_001303281NP_065648Parathyroid hormone (PTH), also called parathormone or parathyrin, is a hormone secreted by the parathyroid glands that regulates the serum calcium through its effects on bone, kidney, and intestine. 1bwx: THE SOLUTION STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 1-39, NMR, 10 STRUCTURES1et1: CRYSTAL STRUCTURE OF HUMAN PARATHYROID HORMONE 1-34 AT 0.9 A RESOLUTION1fvy: SOLUTION STRUCTURE OF THE OSTEOGENIC 1-31 FRAGMENT OF THE HUMAN PARATHYROID HORMONE1hph: STRUCTURE OF HUMAN PARATHYROID HORMONE 1-37 IN SOLUTION1hpy: THE SOLUTION STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 1-34 IN 20% TRIFLUORETHANOL, NMR, 10 STRUCTURES1zwa: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 1-34, NMR, 10 STRUCTURES1zwb: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 2-37, NMR, 10 STRUCTURES1zwc: STRUCTURE OF BOVINE PARATHYROID HORMONE FRAGMENT 1-37, NMR, 10 STRUCTURES1zwd: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 3-37, NMR, 10 STRUCTURES1zwe: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 4-37, NMR, 10 STRUCTURES1zwf: STRUCTURE OF N-TERMINAL ACETYLATED HUMAN PARATHYROID HORMONE, NMR, 10 STRUCTURES1zwg: SUCCINYL HUMAN PARATHYROID HORMONE 4-37, NMR, 10 STRUCTURES Parathyroid hormone (PTH), also called parathormone or parathyrin, is a hormone secreted by the parathyroid glands that regulates the serum calcium through its effects on bone, kidney, and intestine. PTH influences bone remodeling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time. PTH is secreted in response to low blood serum calcium (Ca2+) levels. PTH indirectly stimulates osteoclast activity within the bone matrix (osteon), in an effort to release more ionic calcium (Ca2+) into the blood to elevate a low serum calcium level. The bones act as a (metaphorical) 'bank of calcium' from which the body can make 'withdrawals' as needed to keep the amount of calcium in the blood at appropriate levels despite the ever-present challenges of metabolism, stress, and nutritional variations. PTH is 'a key that unlocks the bank vault' to remove the calcium. PTH is secreted primarily by the chief cells of the parathyroid glands. It is a polypeptide containing 84 amino acids, which is a prohormone. It has a molecular mass around 9500 Da. Its action is opposed by the hormone calcitonin. There are two types of PTH receptors. Parathyroid hormone 1 receptors, activated by the 34 N-terminal amino acids of PTH, are present at high levels on the cells of bone and kidney. Parathyroid hormone 2 receptors are present at high levels on the cells of central nervous system, pancreas, testes, and placenta. The half-life of PTH is about 4 minutes. Disorders that yield too little or too much PTH, such as hypoparathyroidism, hyperparathyroidism, and paraneoplastic syndromes can cause bone disease, hypocalcaemia, and hypercalcaemia. hPTH-(1-34) crystallizes as a slightly bent, long, helical dimer. The extended helical conformation of hPTH-(1-34) is the likely bioactive conformation. The N-terminal fragment 1-34 of parathyroid hormone (PTH) has been crystallized and the structure has been refined to 0.9 Å resolution. Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine: In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of Osteoprotegerin (OPG). Free OPG competitively binds to RANKL as a decoy receptor, preventing RANKL from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates these osteoclast precursors to fuse, forming new osteoclasts, which ultimately enhances bone resorption. Another mechanism to regulate this pathways as PTH does is by estrogen. Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity in the bone marrow, thymus, and peripheral lymphoid organs. In the bone marrow, estrogen downregulates the proliferation of hematopoietic stem cells through an IL-7 dependent mechanism. In the kidney, around 250 mmol of calcium ions are filtered into the glomerular filtrate per day. Most of this (245 mmol/d) is reabsorbed from the tubular fluid, leaving about 5 mmol/d to be excreted in the urine. This reabsorption occurs throughout the tubule (most, 60-70%, of it in the proximal tubule), except in the thin segment of the loop of Henle. Circulating parathyroid hormone only influences the reabsorption that occurs in the distal tubules and the renal collecting ducts (but see Footnote). A more important effect of PTH on the kidney is, however, its inhibition of the reabsorption of phosphate (HPO42−) from the tubular fluid, resulting in a decrease in the plasma phosphate concentration. Phosphate ions form water-insoluble salts with calcium. Thus, a decrease in the phosphate concentration of the blood plasma (for a given total calcium concentration) increases the amount of calcium that is ionized. A third important effect of PTH on the kidney is its stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine.