Calcitonin

  • OMIM: 114130
  • UniProt: P01258
  • MGI: 2151253

The calcitonin ( syn. calcitonin, Thyreocalcitonin ) is a protein that belongs to the group of peptide hormones. It is made with the mammals in the C- cells ( "C" for calcitonin ) of the thyroid gland. They are also called parafollicular cells, since they are next to the follicular epithelial cells of the thyroid gland, the thyroid cells, are located. In other vertebrates, the formation of the ultimobranchial body takes place.

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

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

History

Calcitonin was postulated in 1961 by Copp and Cameron in isolated thyroid and parathyroid glands of dogs. They wrote the calcitonin already a calcium - lowering effect to, associated the origin of the hormone though initially the parathyroid glands to. Three years later it was discovered that it is Calcitonin is a hormone produced by the thyroid gland and 1967 were also the responsible cells, the parafollicular cells, were identified. The parafollicular cells themselves have already been discovered in 1876 in the thyroid glands of dogs.

Structure

The human calcitonin ( hCT ) is a polypeptide consisting of 32 amino acids and has a molecular weight of 3421 daltons.

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

Regulation and effects

The Calcitoninfreisetzung is stimulated by:

  • High calcium concentration in the blood
  • Gastrointestinal hormones pentagastrin

Calcitonin lowers blood calcium levels: It inhibits the release of calcium from the bones ( Activity of osteoclasts is down-regulated ), promotes calcium excretion by the kidney, is the calcium absorption in the gut down. It acts with respect to the calcium level in the blood that is antagonistic to parathormone. The phosphate excretion in the kidney, however, it also increases as parathyroid hormone. Calcitonin in higher doses in humans a diuretic effect. This increased proximal natriuresis is balanced again about 80 minutes after the intravenous Calcitoningabe by increased distal sodium reabsorption. In addition, calcitonin lowers blood phosphate levels by inhibiting the reabsorption of phosphate on the proximal tubule cells of the kidney ( synergistic effect on parathyroid hormone ).

Compared to the other calcium- regulating hormones parathyroid hormone ( PTH) and D hormone ( calcitriol ), however, appears to play a strong secondary role calcitonin.

Medical Application

Calcitonin is a therapeutic option to reduce greatly increased calcium levels due to malignant neoplastic diseases, for the prevention of acute bone loss after about osteoporotic fractures ( fractures) and for the treatment of Paget 's disease ( Osteitis deformans ). They are used subcutaneously, intramuscularly or intravenously. Used medicinally is not the human calcitonin, but a salmon calcitonin.

Side effects and limitations of use

The most common side effects are gastrointestinal disturbances such as nausea and vomiting, and skin redness ( "flush ") in the face. Patients who suffer from hypocalcemia, should not be treated with calcitonin. 2012 were evidence of an increased incidence of malignant tumors ( malignancy ) after long-term application known what led to corresponding restrictions on use; as calcitonin, is not indicated for the treatment such as the post- menopausal osteoporosis, which is designed for a longer duration of treatment.

Blood levels

Calcitonin is used as a tumor marker in the medullary thyroid carcinoma. Normal value for adult is less than 10 ng / dl (equivalent to 2.8 pmol / l). Conversion factor from ng / dL to pmol / l for calcitonin: ng / l × 0.28 = pmol / l A low calcitonin levels there is not probably. Even in healthy calcitonin may be below the detection limit of the currently available tests. Too high a value can be found:

  • Rare in hyperthyroidism
  • The medullary thyroid carcinoma (C- cell carcinoma)
  • At C - cell hyperplasia ( eg as part of multiple endocrine neoplasia, type IIa (MEN IIa ) )
  • In renal insufficiency
  • In cirrhosis
  • Sometimes in neuroendocrine tumors, such as lung
Procalcitonin Protein isoform Human Genome Organisation Mouse Genome Informatics Anatomical Therapeutic Chemical Classification System Euteleostomi Receptor antagonist Paget's disease of bone Menopause Tumormarker
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