Parathyroid hormone 418916 224252475 2008-07-08T00:27:53Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{PBB|geneid=5741}} '''Parathyroid hormone (PTH)''', or '''parathormone''', is secreted by the [[parathyroid gland]]s as a [[polypeptide]] containing 84 [[amino acids]]. It acts to increase the concentration of [[calcium]] (Ca<sup>2+</sup>) in the [[blood]], whereas [[calcitonin]] (a hormone produced by the [[parafollicular cells]] (C cells) of the [[thyroid gland]]) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon [[parathyroid hormone receptor]] in three parts of the body:<ref>{{GeorgiaPhysiology|5/5ch6/s5ch6_11}}</ref> ==Functions== ===Effects on serum calcium (raising)=== {| class="wikitable" | '''Region''' || '''Effect''' |- | [[bone]]s || It enhances the release of calcium from the large reservoir contained in the bones.<ref>{{cite journal | author = Poole K, Reeve J | title = Parathyroid hormone - a bone anabolic and catabolic agent | journal = Curr Opin Pharmacol | volume = 5 | issue = 6 | pages = 612–7 | year = 2005 | pmid = 16181808 | doi = 10.1016/j.coph.2005.07.004}}</ref> [[Bone resorption]] is the normal destruction of bone by [[osteoclast]]s, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to [[osteoblast]]s, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of [[RANKL]], which can bind to osteoclast precursors containing [[RANK]], a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone. |- | [[kidney]] || It enhances active reabsorption of calcium from [[distal tubule]]s<ref It also greatly increases the excretion of Phosphate. As bone is degraded both calcium and phosphate is released. By increasing the calcium:phosphate ratio more calcium is therefore free in the circulation. name="mcgill">http://sprojects.mmi.mcgill.ca/nephrology/presentation/presentation5.htm</ref> and the thick ascending limb. |- | [[intestine]] via kidney || It enhances the absorption of calcium in the [[intestine]] by increasing the production of activated [[vitamin D]]. Vitamin D activation occurs in the kidney. PTH up-regulates the enzyme responsible for 1-alpha [[hydroxylation]] of [[25-hydroxy vitamin D]], converting vitamin D to its active form ([[1,25-dihydroxy vitamin D]]). This activated form of vitamin D affects the absorption of calcium (as Ca<sup>2+</sup> ions) by the intestine via [[calbindin]]. |} PTH was one of the first hormones to be shown to use the G-protein, adenylyl cyclase second messenger system. Normal total plasma calcium level is 9.4mg/dl(8-11) or 2.4mmol/L<ref>guyton</ref> <ref name="metabolism">http://books.google.com/books?id=BxLU6XhZsTAC&pg=RA1-PA281&lpg=RA1-PA281&dq=pth+second+messenger&source=web&ots=5awUECyZo-&sig=EhEGbV9WdI2Xp5Sv5eJQJ_63S3U#PRA1-PA281,M1</ref> . ===Effects on serum phosphate (decrease, with compensation)=== PTH reduces the reabsorption of [[phosphate]] from the [[proximal tubule]] of the [[kidney]]<ref name="mcgill"> </ref> which means more phosphate is excreted through the urine. However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, which is mediated by an increase in activated vitamin D, the absorption of phosphate is not as dependent on vitamin D as is that of calcium. The end result is a small net drop in the serum concentration of phosphate. ==Feedback regulation== Increased calcium concentration in the blood acts (via [[feedback inhibition]]) to decrease PTH secretion by the parathyroid glands. This is achieved by the activation of calcium-sensing receptors located on parathyroid cells.<ref>{{GeorgiaPhysiology|5/5ch6/s5ch6_9}}</ref> ==Syndromes== * A high level of PTH in the blood is known as [[hyperparathyroidism]]. ** If the cause is in the parathyroid gland it is called ''primary hyperparathyroidism''. The causes are parathyroid [[adenoma]], parathyroid [[hyperplasia]] and parathyroid cancer. ** If the cause is outside the gland, it is known as ''secondary hyperparathyroidism''. This can occur in [[chronic renal failure]]. * A low level of PTH in the blood is known as [[hypoparathyroidism]]. Causes include surgical [[misadventure]] (''eg'' inadvertent removal during routine thyroid surgery), [[autoimmune disorder]], and [[inborn errors of metabolism]]. ==Measurements== PTH can be measured in the blood in several different forms: intact PTH; N-terminal PTH; mid-molecule PTH, and C-terminal PTH, and different tests are used in different clinical situations. ==References== {{Reflist|1}} ==See also== * [[Calcium metabolism]] * [[Disorders of calcium metabolism]] * [[Parathyroid hormone-related protein]] ==Further reading== {{refbegin | 2}} {{PBB_Further_reading | citations = *{{cite journal | author=Drüeke TB, Massy ZA |title=Advanced oxidation protein products, parathyroid hormone and vascular calcification in uremia |journal=Blood Purif. |volume=20 |issue= 5 |pages= 494–7 |year= 2003 |pmid= 12207101 |doi= }} *{{cite journal | author=Parfitt AM |title=Parathyroid hormone and periosteal bone expansion |journal=J. Bone Miner. Res. |volume=17 |issue= 10 |pages= 1741–3 |year= 2003 |pmid= 12369776 |doi= }} *{{cite journal | author=Martin TJ |title=Does bone resorption inhibition affect the anabolic response to parathyroid hormone? |journal=Trends Endocrinol. Metab. |volume=15 |issue= 2 |pages= 49–50 |year= 2004 |pmid= 15080150 |doi= }} *{{cite journal | author=Keutmann HT, Sauer MM, Hendy GN, ''et al.'' |title=Complete amino acid sequence of human parathyroid hormone |journal=Biochemistry |volume=17 |issue= 26 |pages= 5723–9 |year= 1979 |pmid= 728431 |doi= }} *{{cite journal | author=Keutmann HT, Niall HD, O'Riordan JL, Potts JT |title=A reinvestigation of the amino-terminal sequence of human parathyroid hormone |journal=Biochemistry |volume=14 |issue= 9 |pages= 1842–7 |year= 1975 |pmid= 1125201| doi=10.1021/bi00680a006}} *{{cite journal | author=Parkinson DB, Thakker RV |title=A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism |journal=Nat. Genet. |volume=1 |issue= 2 |pages= 149–52 |year= 1993 |pmid= 1302009 |doi= 10.1038/ng0592-149 }} *{{cite journal | author=Handt O, Reis A, Schmidtke J |title=Ectopic transcription of the parathyroid hormone gene in lymphocytes, lymphoblastoid cells and tumour tissue |journal=J. Endocrinol. |volume=135 |issue= 2 |pages= 249–56 |year= 1993 |pmid= 1474331 |doi= }} *{{cite journal | author=Tonoki H, Narahara K, Matsumoto T, Niikawa N |title=Regional mapping of the parathyroid hormone gene (PTH) by cytogenetic and molecular studies |journal=Cytogenet. Cell Genet. |volume=56 |issue= 2 |pages= 103–4 |year= 1991 |pmid= 1672845 |doi= }} *{{cite journal | author=Klaus W, Dieckmann T, Wray V, ''et al.'' |title=Investigation of the solution structure of the human parathyroid hormone fragment (1-34) by 1H NMR spectroscopy, distance geometry, and molecular dynamics calculations |journal=Biochemistry |volume=30 |issue= 28 |pages= 6936–42 |year= 1991 |pmid= 2069952| doi=10.1021/bi00242a018}} *{{cite journal | author=Arnold A, Horst SA, Gardella TJ, ''et al.'' |title=Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism |journal=J. Clin. Invest. |volume=86 |issue= 4 |pages= 1084–7 |year= 1990 |pmid= 2212001| doi=10.1172/JCI114811}} *{{cite journal | author=Nussbaum SR, Gaz RD, Arnold A |title=Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone |journal=N. Engl. J. Med. |volume=323 |issue= 19 |pages= 1324–8 |year= 1990 |pmid= 2215618 |doi= }} *{{cite journal | author=Ahn TG, Antonarakis SE, Kronenberg HM, ''et al.'' |title=Familial isolated hypoparathyroidism: a molecular genetic analysis of 8 families with 23 affected persons |journal=Medicine (Baltimore) |volume=65 |issue= 2 |pages= 73–81 |year= 1986 |pmid= 3005800 |doi= }} *{{cite journal | author=Tregear GW, van Rietschoten J, Greene E, ''et al.'' |title=Solid-phase synthesis of the biologically active N-terminal 1 - 34 peptide of human parathyroid hormone |journal=Hoppe-Seyler's Z. Physiol. Chem. |volume=355 |issue= 4 |pages= 415–21 |year= 1975 |pmid= 4474131 |doi= }} *{{cite journal | author=Niall HD, Sauer RT, Jacobs JW, ''et al.'' |title=The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=71 |issue= 2 |pages= 384–8 |year= 1974 |pmid= 4521809| doi=10.1073/pnas.71.2.384}} *{{cite journal | author=Andreatta RH, Hartmann A, Jöhl A, ''et al.'' |title=[Synthesis of sequence 1-34 of human parathyroid hormone] |journal=Helv. Chim. Acta |volume=56 |issue= 1 |pages= 470–3 |year= 1973 |pmid= 4721748 |doi= 10.1002/hlca.19730560139 }} *{{cite journal | author=Jacobs JW, Kemper B, Niall HD, ''et al.'' |title=Structural analysis of human proparathyroid hormone by a new microsequencing approach |journal=Nature |volume=249 |issue= 453 |pages= 155–7 |year= 1974 |pmid= 4833516| doi=10.1038/249155a0}} *{{cite journal | author=Vasicek TJ, McDevitt BE, Freeman MW, ''et al.'' |title=Nucleotide sequence of the human parathyroid hormone gene |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 8 |pages= 2127–31 |year= 1983 |pmid= 6220408| doi=10.1073/pnas.80.8.2127}} *{{cite journal | author=Mayer H, Breyel E, Bostock C, Schmidtke J |title=Assignment of the human parathyroid hormone gene to chromosome 11 |journal=Hum. Genet. |volume=64 |issue= 3 |pages= 283–5 |year= 1983 |pmid= 6885073| doi=10.1007/BF00279412}} *{{cite journal | author=Hendy GN, Kronenberg HM, Potts JT, Rich A |title=Nucleotide sequence of cloned cDNAs encoding human preproparathyroid hormone |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=78 |issue= 12 |pages= 7365–9 |year= 1982 |pmid= 6950381 |doi= }} *{{cite journal | author=Hendy GN, Bennett HP, Gibbs BF, ''et al.'' |title=Proparathyroid hormone is preferentially cleaved to parathyroid hormone by the prohormone convertase furin. A mass spectrometric study |journal=J. Biol. Chem. |volume=270 |issue= 16 |pages= 9517–25 |year= 1995 |pmid= 7721880 |doi= }} }} {{refend}} {{Hormones}} [[Category:Peptide hormones]] [[Category:Hormones of the parathyroid glands]] [[bg:Паратироиден хормон]] [[cs:Parathormon]] [[da:Parathyroideahormon]] [[de:Parathormon]] [[dv:ޕަރަތައިރޮއިޑް ހޯރމޯން]] [[es:Parathormona]] [[fr:Parathormone]] [[it:Paratormone]] [[nl:Parathormoon]] [[ja:パラトルモン]] [[no:PTH]] [[pl:Parathormon]] [[pt:Hormônio da paratireóide]] [[ru:Паратиреоидный гормон]] [[sq:Parathormoni]] [[sk:Paratyroid]] [[sl:Parathormon]] [[fi:Parathormoni]] [[sv:Parathormon]] [[tr:Parathormon]] {{PBB_Controls<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = no | update_citations = yes }}