Calcitonin

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Calcitonin
Calcitonin
Salmon calcitonin according to PDB  2GLH

Existing structural data : 1bku , 1byv , 1bzb , 1fb9 , 2glh

Properties of human protein
Mass / length primary structure 32 amino acids
Precursor ( Procalcitonin , 141 amino acids)
Isoforms 3
Identifier
Gene names CALCA  ; CALC1
External IDs
Drug information
ATC code H05 BA01
Occurrence
Homology family Calcitonin
Parent taxon Euteleostomi

The calcitonin (synonym: calcitonin , Thyreocalcitonin ) is a protein belonging to the group of peptide hormones belongs. In mammals it is formed in the C cells ("C" for calcitonin) of the thyroid gland and secreted by it. They are also known as parafollicular cells because they are located next to the follicular epithelial cells of the thyroid called thyrocytes. In other vertebrates , formation takes place in the ultimobranchial body .

Calcitonin is the opponent to the parathyroid glands formed parathyroid hormone . Both hormones regulate the calcium and phosphate balance in the body. Calcitonin has a calcium-lowering effect.

The " calcitonin gene-related peptide " (CGRP) is related to calcitonin . Both go back to a common primary mRNA transcript (both are encoded on the CALCA gene). Through tissue-specific alternative splicing , calcitonin is predominantly formed in the thyroid gland, while mainly CGRP is produced in sensory neurons in the central nervous system and in the peripheral nervous system .

history

Calcitonin was postulated in 1961 by Copp and Cameron in isolated thyroid and parathyroid glands of dogs . They already attributed a calcium-lowering effect to calcitonin, but initially assigned the origin of the hormone to the parathyroid glands. Three years later it was discovered that calcitonin is a hormone of the thyroid gland and in 1967 the cells responsible for it, the parafollicular cells, could also be identified. The parafollicular cells themselves were discovered in the thyroid glands of dogs as early as 1876.

structure

Human calcitonin (hCT) is a polypeptide that consists of 32 amino acids and has a molecular mass of 3421  Daltons .

An intramolecular disulfide bridge between Cys-1 and Cys-7 and an amidated C-terminus (prolinamide) are important for biological activity. CT (8-32) without a disulfide bridge binds to the calcitonin receptor , but does not cause receptor activation, but acts as a competitive antagonist .

Regulation and Effect

Calcitonin release is stimulated by:

  • high levels of calcium in the blood
  • gastrointestinal hormones

Calcitonin lowers blood calcium levels. By reducing the activity of the osteoclasts, it inhibits the release of calcium from the bones, promotes calcium excretion via the kidneys and reduces calcium absorption in the intestine. With regard to the calcium level in the blood, it has an antagonistic effect on the parathyroid hormone. However, it also increases phosphate excretion in the kidneys, as does parathyroid hormone. Calcitonin has a diuretic effect in humans in higher doses. This increased proximal natriuresis is compensated by increased distal sodium reabsorption about 80 minutes after the intravenous administration of calciton. In addition, calcitonin lowers the phosphate level in the blood by inhibiting the reabsorption of phosphate via the proximal tubular cells of the kidney (synergistic effect with the parathyroid hormone).

Compared to the other calcium-regulating hormones parathyroid hormone (PTH) and D-hormone ( calcitriol ), calcitonin seems to play a very minor role.

Medical application

Calcitonin is indicated therapeutically for lowering calcium levels greatly increased as a result of malignant neoplastic diseases, for the prevention of acute bone loss include osteoporosis -related bone fractures (fractures) and for the treatment of Paget's disease ( Paget's disease of bone ). It is used subcutaneously , intramuscularly or intravenously . It is not human calcitonin that is used medicinally, but a salmon calcitonin.

Side effects and restrictions on use

The most common side effects are gastrointestinal disturbances such as nausea and vomiting as well as reddening of the skin (" flush ") on the face. Calcitonin should not be used in patients with hypocalcaemia . In 2012 there were indications of an increased incidence of malignant tumors ( malignancy ) after long-term use, which led to corresponding restrictions in use; Calcitonin, for example , is not indicated for the treatment of post- menopausal osteoporosis, which is designed for a longer treatment period.

Blood levels

Calcitonin is used as a tumor marker in medullary thyroid carcinoma . The normal value in adults is less than 10 ng / l (corresponds to 2.8 pmol / l). Conversion factor from ng / l to pmol / l for calcitonin: ng / l × 0.28 = pmol / l. There is probably no such thing as a calcitonin level that is too low. Even in healthy people, calcitonin can be below the detection limit of the currently available tests. One finds a value that is too high:

See also

literature

  • M. Azria: Calcitonins. Physiology and Pharmacology. Karger, Basel et al. 1989, ISBN 3-8055-4851-6 .
  • E. Keck: Calcitonin and Calcitonin Therapy. 3., completely reworked. Edition. Stuttgart 1996, ISBN 3-8047-1478-1 .
  • F. Raue, A. Grauer In: L. Thomas (Ed.): Labor und Diagnose. 6th edition. TH-Books, 2005, ISBN 3-9805215-5-9 .
  • T. Kreuzig: Short textbook biochemistry. 12th edition. Urban & Fischer, 2006, ISBN 3-437-41774-6 .

Individual evidence

  1. ^ DH Copp et al .: Demonstration of a hypocalcemic factor (calcitonin) in commercial parathyroid extract. In: Science. 134, 1961 Dec 22, p. 2038, PMID 13881212 .
  2. ^ J. Vague: History of Endocrinology after World War II. In: R. Toellner: Illustrated history of medicine. Volume 6, Andreas Verlag Salzburg 1992, ISBN 3-86070-204-1 .
  3. ^ GV Foster et al.: Thyroid Origin of Calcitonin. In: Nature. 202, 1964 Jun 27, pp. 1303-1305, PMID 14210962 .
  4. ^ SD Tauber: The ultimobranchial origin of thyrocalcitonin. In: Proc. Natl. Acad. Sci. USA . 58 (4), 1967 Oct, pp. 1684-1687, PMID 5237896 .
  5. ^ EC Baber: Contributions to the minute anatomy of the thyroid gland of the dog. In: Phil Trans R Soc. 166 (1876), pp. 557-568. ( Full text )
  6. ↑ T. Hagedorn: Morphological and morphometric investigations to distinguish sporadic and hereditary C-cell hyperplasia . Dissertation . 2006 PDF version .
  7. ↑ UniProt P01258
  8. ↑ Rote-Hand-Brief: Important information on the connection between calcitonin and malignancy , August 15, 2012 (PDF; 308 kB), retrieved from the website of the Drug Commission of the German Medical Association (AkdÄ).

Commercial preparations

Monopreparations

CalciHexal (D), Forcaltonin (A), Karil (D), Miacalcic (CH), Ucecal (A), numerous generics (D, A)

Web links