Calcitonin 467058 224252576 2008-07-08T00:28:33Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{PBB|geneid=796}} '''Calcitonin''' is a 32-amino acid polypeptide [[hormone]] that is produced in [[human]]s primarily by the [[Parafollicular cell|parafollicular]] (also known as C-cells) of the [[thyroid]], and in many other animals in the [[ultimobranchial body]].<ref>[http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch6/s5ch6_21.htm Sect. 5, Ch. 6: Anatomy, Structure, and Synthesis of Calcitonin (CT)<!-- Bot generated title -->]</ref> It acts to reduce blood [[calcium]] (Ca<sup>2+</sup>), opposing the effects of [[parathyroid hormone]] (PTH) <ref name=boron> Medical Physiology, Boron & Boulpaep, ISBN 1-4160-2328-3, Elsevier Saunders 2005. Updated edition. Endocrine system chapter. </ref> It has been found in [[fish]], [[reptile]]s, [[bird]]s, and [[mammal]]s. Its importance in humans has not been as well established as its importance in other animals.<ref>[http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch6/s5ch6_23.htm Sect. 5, Ch. 6: Biological Actions of CT<!-- Bot generated title -->]</ref> ==Biosynthesis== Calcitonin is formed by the [[proteolytic]] cleavage of a larger [[prepropeptide]], which is the product of the CALC1 gene ({{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]] (Ca<sup>2+</sup>) and [[phosphorus]] [[metabolism]]. In many ways, calcitonin has the counter effects of [[parathyroid hormone]] (PTH). To be specific, calcitonin reduces blood Ca<sup>2+</sup> levels in three ways: * Decreasing Ca<sup>2+</sup> absorption by the [[intestines]]<ref>[http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch6/s5ch6_26.htm Sect. 5, Ch. 6: Effects of CT on the Small Intestine<!-- Bot generated title -->]</ref> * Decreasing [[osteoclast]] activity in [[bone]]s<ref>[http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch6/s5ch6_24.htm Sect. 5, Ch. 6: Effects of CT on Bone<!-- Bot generated title -->]</ref> * Decreasing Ca<sup>2+</sup> and phosphate reabsorption by the [[kidney]] tubules<ref>[http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch6/s5ch6_25.htm Sect. 5, Ch. 6: Effects of CT on Kidneys<!-- Bot generated title -->]</ref> ==Actions== Its actions, in a broad sense, are: * Bone mineral metabolism: ::- Prevent postprandial [[hypercalcemia]] resulting from absorption of Ca<sup>2+</sup> from foods during a meal ::- Promote [[mineralization]] of skeletal bone ::- Protect against Ca<sup>2+</sup> loss from skeleton during periods of Ca<sup>2+</sup> stress such as [[pregnancy]] and [[lactation]] * [[Vitamin D]] regulation * A [[satiety]] hormone: ::- Inhibit food intake in rats and monkeys ::- May have [[Central nervous system|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 [[G proteins#Alpha subunits|G<sub>s</sub>]] to [[adenylyl cyclase]] and thereby to the generation of [[cyclic AMP|cAMP]] in target cells. ==History== Calcitonin was purified in 1962 by Copp and Cheney.<ref>Copp DH, Cheney B. ''Calcitonin-a hormone from the parathyroid, which lowers the calcium-level of the blood.'' Nature 1962;193:381-2. PMID 13881213</ref> While it was initially considered a secretion of the [[parathyroid gland]]s, 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 metastase]]s * Phantom limb pain<ref>"Calcitonin in phantom limb pain": Ann Pharmacother. 1999 Apr;33(4):499-501 PMID: 10332543</ref> The following information is from the UK Electronic Medicines Compendium<ref name="UKEMC">http://emc.medicines.org.uk/ UK Electronic Medicines Compendium</ref> ===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.<ref name="UKEMC"/> ==Use of calcitonin in osteoarthritis== 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.”<ref>{{cite web | last = Kleinman | first = Denise Mann | title = Oral Calcitonin May Delay Onset of Joint Disease and Relieve Pain of OA | work = Musculoskelital Report | publisher = | date = 2006-01-04 | url = http://www.mskreport.com/articles.cfm?ArticleID=515 | accessdate = 2008-05-20 }}</ref> ==See also== * [[Procalcitonin]] * [[Miacalcin]] ==References== {{reflist}} ==Further reading== {{refbegin | 2}} {{PBB_Further_reading | citations = *{{cite journal | author=MacIntyre I, Alevizaki M, Bevis PJ, Zaidi M |title=Calcitonin and the peptides from the calcitonin gene |journal=Clin. Orthop. Relat. Res. |volume= &na;|issue= 217 |pages= 45–55 |year= 1987 |pmid= 3549095| doi=10.1097/00003086-198704000-00007}} *{{cite journal | author=Di Angelantonio S, Giniatullin R, Costa V, ''et al.'' |title=Modulation of neuronal nicotinic receptor function by the neuropeptides CGRP and substance P on autonomic nerve cells |journal=Br. J. Pharmacol. |volume=139 |issue= 6 |pages= 1061–73 |year= 2004 |pmid= 12871824 |doi= 10.1038/sj.bjp.0705337 }} *{{cite journal | author=Findlay DM, Sexton PM |title=Calcitonin |journal=Growth Factors |volume=22 |issue= 4 |pages= 217–24 |year= 2005 |pmid= 15621724 |doi= 10.1080/08977190410001728033 }} *{{cite journal | author=Sponholz C, Sakr Y, Reinhart K, Brunkhorst F |title=Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature |journal=Critical care (London, England) |volume=10 |issue= 5 |pages= R145 |year= 2007 |pmid= 17038199 |doi= 10.1186/cc5067 }} *{{cite journal | author=Schneider HG, Lam QT |title=Procalcitonin for the clinical laboratory: a review |journal=Pathology |volume=39 |issue= 4 |pages= 383–90 |year= 2007 |pmid= 17676478 |doi= 10.1080/00313020701444564 }} }} {{refend}} ==External links== * {{MeshName|Calcitonin}} {{Hormones}} {{Neuropeptides}} [[Category:Peptide hormones]] [[Category:Hormones of the thyroid gland]] [[ar:كالسيتونين]] [[bg:Калцитонин]] [[cs:Kalcitonin]] [[de:Calcitonin]] [[dv:ކެލްސިޓޯނިން]] [[es:Calcitonina]] [[fr:Calcitonine]] [[it:Calcitonina]] [[nl:Calcitonine]] [[ja:カルシトニン]] [[no:Kalsitonin]] [[pl:Kalcytonina]] [[pt:Calcitonina]] [[sk:Kalcitonín]] [[sl:Kalcitonin]] [[sr:Калцитонин]] [[fi:Kalsitoniini]] [[tr:Kalsitonin]] <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = yes | update_citations = yes }}