Calcitonin

Calcitonin/calcitonin-related polypeptide, alpha
Identifiers
Symbol(s)	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 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. It acts to reduce blood calcium (Ca²⁺), opposing the effects of parathyroid hormone (PTH)

note: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:

The ultimobranchial body or gland is a small organ found in the neck region of many animals.

In humans, the ultimobranchial body is an embryological structure that gives rise to the calcitonin-producing cells—also called parafollicular cells or clear cells—of the thyroid gland. In humans, this body is a derivative of the ventral recess of the fourth pharyngeal pouch (or fifth)

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.

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 reduces blood Ca²⁺ levels in three ways:

• Decreasing Ca²⁺ absorption by the intestines
• Decreasing osteoclast activity in bones
• Decreasing Ca²⁺ and phosphate reabsorption by the kidney tubules

Actions

Its actions, in a broad sense, are:

• Bone mineral metabolism:

- Prevent postprandial hypercalcemia resulting from absorption of Ca²⁺ from foods during a meal

- Promote mineralization of skeletal bone

- Protect against Ca²⁺ loss from skeleton during periods of Ca²⁺ stress such as pregnancy and lactation

• 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 G_s to adenylyl cyclase and thereby to the generation of cAMP in target cells.

History

Calcitonin was purified in 1962 by Copp and Cheney. 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 pain

The following information is from the UK Electronic Medicines Compendium

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.

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.”

See also

• Procalcitonin
• Miacalcin

References

ISBN links support NWE through referral fees

• Wood, D., and T. G. Odle. 2006. In J. L. Longe, The Gale Encyclopedia of Cancer. Detroit, MI: Gale. ISBN 1414403623.

J. Biochem, 1976, Vol. 79, No. 2 353-359

© 1976 Japanese Biochemical Society research-article Amino Acid Sequence of Eel Calcitonin Toshiharu NODA1 and Kozo NARITA

http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=SM00113

Simple Modular Architecture Research Tool

Further reading

• MacIntyre I, Alevizaki M, Bevis PJ, Zaidi M (1987). Calcitonin and the peptides from the calcitonin gene.. Clin. Orthop. Relat. Res. (217): 45-55.
• 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.
• Findlay DM, Sexton PM (2005). Calcitonin.. Growth Factors 22 (4): 217-24.
• 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.
• Schneider HG, Lam QT (2007). Procalcitonin for the clinical laboratory: a review.. Pathology 39 (4): 383-90.

Hormones and endocrine glands

Hypothalamus: GnRH - TRH - CRH - GHRH - somatostatin - dopamine | Posterior pituitary: vasopressin - oxytocin | Anterior pituitary: GH - ACTH - TSH - LH - FSH - prolactin - MSH - endorphins - lipotropin Thyroid: T3 and T4 - calcitonin | Parathyroid: PTH | Adrenal medulla: epinephrine - norepinephrine | Adrenal cortex: aldosterone - cortisol - DHEA | Pancreas: glucagon- insulin - somatostatin | Ovary: estradiol - progesterone - inhibin - activin | Testis: testosterone - AMH - inhibin | Pineal gland: melatonin | Kidney: renin - EPO - calcitriol - prostaglandin | Heart atrium: ANP Stomach: gastrin | Duodenum: CCK - GIP - secretin - motilin - VIP | Ileum: enteroglucagon | Liver: IGF-1 Placenta: hCG - HPL - estrogen - progesterone Adipose tissue: leptin, adiponectin Target-derived NGF, BDNF, NT-3

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