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14-September-2008 18:02:48 - hormone Parathyroid hormone PDB rendering based on 1bwx. Available structures: 1bwx, 1et1, 1fvy, 1hph, 1hpy, 1zwa, 1zwb, 1zwc, 1zwd, 1zwe, 1zwf, 1zwg Identifiers Symbols PTH; External IDs OMIM: 168450 MGI: 97799 HomoloGene: 266 Gene ontology Molecular function: hormone activity Cellular component: extracellular region Biological process: skeletal development cellular calcium ion homeostasis G-protein coupled receptor protein signaling pathway cell-cell signaling lactation induction of apoptosis by hormones bone resorption cAMP metabolic process RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 5741 19226 Ensembl ENSG00000152266 ENSMUSG00000059077 Uniprot P01270 n/a Refseq NM_000315 mRNA NP_000306 protein NM_020623 mRNA NP_065648 protein Location Chr 11: 13.47 - 13.47 Mb Chr 7: 113.18 - 113.18 Mb Pubmed search 1 2 Parathyroid hormone PTH, or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium Ca2+ 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:1 Contents 1 Functions 1.1 Effects on serum calcium raising 1.2 Effects on serum phosphate decrease, with compensation 2 Feedback regulation 3 Syndromes 4 Measurements 5 References 6 See also 7 Further reading Functions Effects on serum calcium raising Region Effect bones It enhances the release of calcium from the large reservoir contained in the bones.2 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, 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 tubules3 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 25-Hydroxyvitamin D3 1-alpha-hydroxylase, 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 Ca2+ 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/dl8-11 or 2.4mmol/L4 5 . Effects on serum phosphate decrease, with compensation PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney6 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.7 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 ^ Physiology at MCG 5/5ch6/s5ch6_11 ^ Poole K, Reeve J 2005. Parathyroid hormone - a bone anabolic and catabolic agent. Curr Opin Pharmacol 5 6: 612-7. doi:10.1016/j.coph.2005.07.004. PMID 16181808. ^ http://sprojects.mmi.mcgill.ca/nephrology/presentation/presentation5.htm ^ guyton ^ http://books.google.com/books?id=BxLU6XhZsTACpg=RA1-PA281lpg=RA1-PA281dq=pth+second+messengersource=webots=5awUECyZo-sig=EhEGbV9WdI2Xp5Sv5eJQJ_63S3U#PRA1-PA281,M1 ^ ^ Physiology at MCG 5/5ch6/s5ch6_9 See also Calcium metabolism Disorders of calcium metabolism Parathyroid hormone-related protein Further reading Drüeke TB, Massy ZA 2003. Advanced oxidation protein products, parathyroid hormone and vascular calcification in uremia. Blood Purif. 20 5: 494-7. PMID 12207101. Parfitt AM 2003. Parathyroid hormone and periosteal bone expansion. J. Bone Miner. Res. 17 10: 1741-3. PMID 12369776. Martin TJ 2004. Does bone resorption inhibition affect the anabolic response to parathyroid hormone?. Trends Endocrinol. Metab. 15 2: 49-50. PMID 15080150. Keutmann HT, Sauer MM, Hendy GN, et al. 1979. Complete amino acid sequence of human parathyroid hormone. Biochemistry 17 26: 5723-9. PMID 728431. Keutmann HT, Niall HD, O'Riordan JL, Potts JT 1975. A reinvestigation of the amino-terminal sequence of human parathyroid hormone. Biochemistry 14 9: 1842-7. doi:10.1021/bi00680a006. PMID 1125201. Parkinson DB, Thakker RV 1993. A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism. Nat. Genet. 1 2: 149-52. doi:10.1038/ng0592-149. PMID 1302009. Handt O, Reis A, Schmidtke J 1993. Ectopic transcription of the parathyroid hormone gene in lymphocytes, lymphoblastoid cells and tumour tissue. J. Endocrinol. 135 2: 249-56. PMID 1474331. Tonoki H, Narahara K, Matsumoto T, Niikawa N 1991. Regional mapping of the parathyroid hormone gene PTH by cytogenetic and molecular studies. Cytogenet. Cell Genet. 56 2: 103-4. PMID 1672845. Klaus W, Dieckmann T, Wray V, et al. 1991. Investigation of the solution structure of the human parathyroid hormone fragment 1-34 by 1H NMR spectroscopy, distance geometry, and molecular dynamics calculations. Biochemistry 30 28: 6936-42. doi:10.1021/bi00242a018. PMID 2069952. Arnold A, Horst SA, Gardella TJ, et al. 1990. Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. J. Clin. Invest. 86 4: 1084-7. doi:10.1172/JCI114811. PMID 2212001. Nussbaum SR, Gaz RD, Arnold A 1990. Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone. N. Engl. J. Med. 323 19: 1324-8. PMID 2215618. Ahn TG, Antonarakis SE, Kronenberg HM, et al. 1986. Familial isolated hypoparathyroidism: a molecular genetic analysis of 8 families with 23 affected persons. Medicine Baltimore 65 2: 73-81. PMID 3005800. Tregear GW, van Rietschoten J, Greene E, et al. 1975. Solid-phase synthesis of the biologically active N-terminal 1 - 34 peptide of human parathyroid hormone. Hoppe-Seyler's Z. Physiol. Chem. 355 4: 415-21. PMID 4474131. Niall HD, Sauer RT, Jacobs JW, et al. 1974. The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone. Proc. Natl. Acad. Sci. U.S.A. 71 2: 384-8. doi:10.1073/pnas.71.2.384. PMID 4521809. Andreatta RH, Hartmann A, Jöhl A, et al. 1973. Synthesis of sequence 1-34 of human parathyroid hormone. Helv. Chim. Acta 56 1: 470-3. doi:10.1002/hlca.19730560139. PMID 4721748. Jacobs JW, Kemper B, Niall HD, et al. 1974. Structural analysis of human proparathyroid hormone by a new microsequencing approach. Nature 249 453: 155-7. doi:10.1038/249155a0. PMID 4833516. Vasicek TJ, McDevitt BE, Freeman MW, et al. 1983. Nucleotide sequence of the human parathyroid hormone gene. Proc. Natl. Acad. Sci. U.S.A. 80 8: 2127-31. doi:10.1073/pnas.80.8.2127. PMID 6220408. Mayer H, Breyel E, Bostock C, Schmidtke J 1983. Assignment of the human parathyroid hormone gene to chromosome 11. Hum. Genet. 64 3: 283-5. doi:10.1007/BF00279412. PMID 6885073. Hendy GN, Kronenberg HM, Potts JT, Rich A 1982. Nucleotide sequence of cloned cDNAs encoding human preproparathyroid hormone. Proc. Natl. Acad. Sci. U.S.A. 78 12: 7365-9. PMID 6950381. Hendy GN, Bennett HP, Gibbs BF, et al. 1995. Proparathyroid hormone is preferentially cleaved to parathyroid hormone by the prohormone convertase furin. A mass spectrometric study. J. Biol. Chem. 270 16: 9517-25. PMID 7721880. v d e Endocrine system: hormones/endocrine glands Peptide hormones, Steroid hormones Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α FSH, LH, TSH, GH, prolactin, POMC ACTH, MSH, endorphins, lipotropin Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone T3 and T4 - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin pregnancy Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor IGF-1, IGF-2 Target-derived NGF, BDNF, NT-3 Retrieved from http://en..org/wiki/Parathyroid_hormone Categories: Genes on chromosome 11 | Human proteins | Peptide hormones | Hormones of the parathyroid glands Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages العربية БългарÑ?ки ÄŒesky Dansk Deutsch Þ‹Þ¨ÞˆÞ¬Þ€Þ¨Þ„Þ¦Þ?Þ° Español Français Italiano Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Polski Português РуÑ?Ñ?кий Shqip SlovenÄ?ina SlovenÅ¡Ä?ina Suomi Svenska Türkçe This page was last modified on 5 September 2008, at 13:08
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