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14-September-2008 18:02:45 - Calcitonin Calcitonin/calcitonin-related polypeptide, alpha Identifiers Symbols CALCA; CALC1; CGRP; CGRP-I; CGRP1; CT; KC; MGC126648 External IDs OMIM: 114130 MGI: 2151253 HomoloGene: 1319 Gene ontology Molecular function: hormone activity Cellular component: extracellular region extracellular space soluble fraction endoplasmic reticulum Biological process: skeletal development G-protein signaling, coupled to cAMP nucleotide second messenger adenylate cyclase activation phospholipase C activation elevation of cytosolic calcium ion concentration cell-cell signaling blood pressure regulation RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 796 12310 Ensembl ENSG00000110680 ENSMUSG00000030669 Uniprot P01258 Q99JA0 Refseq NM_001033952 mRNA NP_001029124 protein NM_001033954 mRNA NP_001029126 protein Location Chr 11: 14.94 - 14.95 Mb Chr 7: 114.42 - 114.43 Mb Pubmed search 1 2 Calcitonin is a 32-amino acid linear polypeptide hormone that is produced in humans primarily by the parafollicular also known as C-cells of the thyroid, and in many other animals in the ultimobranchial body.1 It acts to reduce blood calcium Ca2+, opposing the effects of parathyroid hormone PTH.2 It has been found in fish, reptiles, birds, and mammals. Its importance in humans has not been as well established as its importance in other animals.3 Contents 1 Biosynthesis 2 Physiology 3 Actions 4 Receptor 5 History 6 Pharmacology 6.1 General characteristics of the active substance 6.2 Characteristics in patients 6.3 Preclinical safety data 7 Pharmaceutical manufacture 8 Uses of calcitonin 8.1 Treatments 8.2 Diagnostics 9 See also 10 References 11 Further reading 12 External links Biosynthesis Calcitonin is formed by the proteolytic cleavage of a larger prepropeptide, which is the product of the CALC1 gene CALCA. The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid precursor protein, calcitonin gene-related peptide, and the precursor of adrenomedullin. Physiology The hormone participates in calcium Ca2+ and phosphorus metabolism. In many ways, calcitonin has the counter effects of parathyroid hormone PTH. To be specific, calcitonin affects blood Ca2+ levels in three ways: Inhibits Ca2+ absorption by the intestines 4 Inhibits osteoclast activity in bones5 Inhibits Ca2+ and phosphate reabsorption by the kidney tubules6 Actions Its actions, in a broad sense, are: Bone mineral metabolism: - Protect against Ca2+ loss from skeleton during periods of Ca2+ stress such as pregnancy and lactation Serum calcium level regulation - Prevent postprandial hypercalcemia resulting from absorption of Ca2+ from foods during a meal - Vitamin D regulation A satiety hormone: - Inhibit food intake in rats and monkeys - May have CNS action involving the regulation of feeding and appetite Receptor The calcitonin receptor, found primarily on osteoclasts, is a G protein-coupled receptor, which is coupled by Gs to adenylyl cyclase and thereby to the generation of cAMP in target cells. History Calcitonin was purified in 1962 by Copp and Cheney.7 While it was initially considered a secretion of the parathyroid glands, it was later identified as the secretion of the C-cells of the thyroid gland. Pharmacology Salmon calcitonin is used for the treatment of: Postmenopausal osteoporosis Hypercalcaemia Paget's disease Bone metastases Phantom limb pain8 The following information is from the UK Electronic Medicines Compendium9 General characteristics of the active substance Salmon calcitonin is rapidly absorbed and eliminated. Peak plasma concentrations are attained within the first hour of administration. Animal studies have shown that calcitonin is primarily metabolised via proteolysis in the kidney following parenteral administration. The metabolites lack the specific biological activity of calcitonin. Bioavailability following subcutaneous and intramuscular injection in humans is high and similar for the two routes of administration 71% and 66%, respectively. Calcitonin has short absorption and elimination half-lives of 10-15 minutes and 50-80 minutes, respectively. Salmon calcitonin is primarily and almost exclusively degraded in the kidneys, forming pharmacologically-inactive fragments of the molecule. Therefore, the metabolic clearance is much lower in patients with end-stage renal failure than in healthy subjects. However, the clinical relevance of this finding is not known. Plasma protein binding is 30% to 40%. Characteristics in patients There is a relationship between the subcutaneous dose of calcitonin and peak plasma concentrations. Following parenteral administration of 100 IU calcitonin, peak plasma concentration lies between about 200 and 400 pg/ml. Higher blood levels may be associated with increased incidence of nausea and vomiting. Preclinical safety data Conventional long-term toxicity, reproduction, mutagenicity, and carcinogenicity studies have been performed in laboratory animals. Salmon calcitonin is devoid of embryotoxic, teratogenic, and mutagenic potential. An increased incidence of pituitary adenomas has been reported in rats given synthetic salmon calcitonin for 1 year. This is considered a species-specific effect and of no clinical relevance. Salmon calcitonin does not cross the placental barrier. In lactating animals given calcitonin, suppression of milk production has been observed. Calcitonin is secreted into the milk. Pharmaceutical manufacture Calcitonin was extracted from the Ultimobranchial glands thyroid-like glands of fish, particularly salmon. Salmon calcitonin resembles human calcitonin, but is more active. At present, it is produced either by recombinant DNA technology or by chemical peptide synthesis. The pharmacological properties of the synthetic and recombinant peptides have been demonstrated to be qualitatively and quantitatively equivalent.9 Uses of calcitonin Treatments Calcitonin can be used therapeutically for the treatment of hypercalcemia or osteoporosis. Oral calcitonin may have a chondroprotective role in osteoarthritis OA, according to data in rats presented in December, 2005, at the 10th World Congress of the Osteoarthritis Research Society International OARSI in Boston, Massachusetts. Although calcitonin is an established antiresorptive agent, its disease-modifying effects on chondrocytes and cartilage metabolisms have not been well established until now. This new study, however, may help to explain how calcitonin affects osteoarthritis. Calcitonin acts both directly on osteoclasts, resulting in inhibition of bone resorption and following attenuation of subchondral bone turnover, and directly on chondrocytes, attenuating cartilage degradation and stimulating cartilage formation, says researcher Morten Karsdal, MSC, PhD, of the department of pharmacology at Nordic Bioscience in Herlev, Denmark. Therefore, calcitonin may be a future efficacious drug for OA.10 Diagnostics It may be used diagnostically as a tumor marker for a form of thyroid cancer medullary thyroid adenocarcinoma, in which high calcitonin levels may be present and elevated levels after surgery may indicate recurrence. It may even be used on biopsy samples from suspicious lesions e.g. swollen lymph nodes to establish whether they are metastasis of the original cancer. See also Procalcitonin Miacalcin References ^ Costoff A. Sect. 5, Ch. 6: Anatomy, Structure, and Synthesis of Calcitonin CT. Endocrinology: hormonal control of calcium and phosphate. Medical College of Georgia. Retrieved on 2008-08-07. ^ Boron WF, Boulpaep EL 2004. Endocrine system chapter, Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. ISBN 1-4160-2328-3. ^ Costoff A. Sect. 5, Ch. 6: Biological Actions of CT. Medical College of Georgia. Retrieved on 2008-08-07. ^ Costoff A. Sect. 5, Ch. 6: Effects of CT on the Small Intestine. Medical College of Georgia. Retrieved on 2008-08-07. ^ Costoff A. Sect. 5, Ch. 6: Effects of CT on Bone. Medical College of Georgia. Retrieved on 2008-08-07. ^ Carney SL 1997. Calcitonin and human renal calcium and electrolyte transport. Miner Electrolyte Metab 23 1: 43-7. PMID 9058369. ^ Copp DH, Cheney B January 1962. Calcitonin-a hormone from the parathyroid which lowers the calcium-level of the blood. Nature 193: 381-2. doi:10.1038/193381a0. PMID 13881213. ^ Wall GC, Heyneman CA April 1999. Calcitonin in phantom limb pain. Ann Pharmacother 33 4: 499-501. doi:10.1345/aph.18204. PMID 10332543. ^ a b Electronic Medicines Compendium. Retrieved on 2008-08-07. ^ Kleinman DM 2006-01-04. Oral Calcitonin May Delay Onset of Joint Disease and Relieve Pain of OA. Musculoskeletal Report. Musculoskeletal Report, LLC. Retrieved on 2008-08-07. Further reading MacIntyre I, Alevizaki M, Bevis PJ, Zaidi M 1987. Calcitonin and the peptides from the calcitonin gene. Clin. Orthop. Relat. Res. na; 217: 45-55. doi:10.1097/00003086-198704000-00007. PMID 3549095. Di Angelantonio S, Giniatullin R, Costa V, et al. 2004. Modulation of neuronal nicotinic receptor function by the neuropeptides CGRP and substance P on autonomic nerve cells. Br. J. Pharmacol. 139 6: 1061-73. doi:10.1038/sj.bjp.0705337. PMID 12871824. Findlay DM, Sexton PM 2005. Calcitonin. Growth Factors 22 4: 217-24. doi:10.1080/08977190410001728033. PMID 15621724. Sponholz C, Sakr Y, Reinhart K, Brunkhorst F 2007. Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature. Critical care London, England 10 5: R145. doi:10.1186/cc5067. PMID 17038199. Schneider HG, Lam QT 2007. Procalcitonin for the clinical laboratory: a review. Pathology 39 4: 383-90. doi:10.1080/00313020701444564. PMID 17676478. External links MeSH Calcitonin 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 v d e Peptides: neuropeptides Hypothalamic Somatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC ACTH, MSH, Lipotropin Gastrointestinal hormones Cholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide Other hormones Vasopressin - Calcitonin - Other Angiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins Bradykinin, Tachykinins - Neuromedin B, N, U - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide Retrieved from http://en..org/wiki/Calcitonin Categories: Genes on chromosome 11 | Human proteins | Peptide hormones | Hormones of the thyroid glandHidden category: Protein pages needing a picture 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 Deutsch Þ‹Þ¨ÞˆÞ¬Þ€Þ¨Þ„Þ¦Þ?Þ° Español Français Italiano Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Polski Português SlovenÄ?ina SlovenÅ¡Ä?ina СрпÑ?ки / Srpski Suomi Türkçe This page was last modified on 11 September 2008, at 18:00
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