Calcitonins and Calcitonin Precursors Peptides Products

Calcitonins and Calcitonin Precursors Peptides

Definition
Calcitonin is a 32-amino acid linear polypeptide hormone produced primarily by the parafollicular cells in humans and ultimobranchial body in many other animals1. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH). Calcitonin is a product of the CALC1 gene and is initially produced as a precursor¹.

Discovery
Calcitonin was purified in 1962 by Copp and Cheney². 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 ³ .

Classification
CALC1 gene belongs to a superfamily of related protein hormone precursors that includes islet amyloid precursor protein, calcitonin gene-related peptide, and the precursor of adrenomedullin ⁴ .

Structural Characteristics
Human calcitonin is a 32 amino acid peptide and is formed from procalcitonin (Cleavage products: Calcitonin, Katalin and a protein fragment)⁵. It has an N-terminal disulphide bridge and a C-terminal proline amide residue, shown to potently inhibit bone resorption5. Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called calcitonin gene-related peptide (CGRP) ⁵.

Mode of action
Calcitonin exerts its functions by binding to calcitonin receptor that is a G-protein coupled receptor. Upon binding, the receptor triggers the formation of cAMP, a second messenger which in turn activates various signaling pathways in the target cell (Eg: Osteoblasts) ⁶ .

Functions
Calcitonin is mainly involved in the metabolism of Ca and phosphorous in the cell. Calcitonin secretion is stimulated by rise in Ca levels in the body. It inhibits Ca intake by the intestine and also prevent loss of Ca from the bones during pregnancy and lactation⁷It also inhibits osteoclast activity in the bones8. This property of calcitonin is utilized for treatment of osteoporosis and osteoarthritis and recently has been tried for bone metastasis1.Procalcitonin is released during severe infection where it is involved in Ca homeostasis. It is also used as a marker for sepsis⁸.

References

1.     Inzerillo AM, Zaidi M, Huang CL (2004). Calcitonin: physiological actions and clinical applications. J Pediatr Endocrinol Metab., 17(7), 931-40.

2.     Copp DH, Cheney B (1962). Calcitonin-a hormone from the parathyroid which lowers the calcium-level of the blood. Nature, 193, 381–2.

3.     Stevenson JC, Evans IM (1981). Pharmacology and therapeutic use of calcitonin. Drugs, 21(4), 257-72.

4.     Zaidi M, Inzerillo AM, Moonga BS, Bevis PJ, Huang CL (2002). Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS, Bone, 30(5), 655-63.

5.     Andreotti G, Méndez BL, Amodeo P, Morelli MA, Nakamuta H, Motta A (2006). "Structural determinants of salmon calcitonin bioactivity: the role of the Leu-based amphipathic alpha-helix". J. Biol. Chem., 281 (34), 24193–203.

6.     Purdue BW, Tilakaratne N, Sexton PM (2002). Molecular pharmacology of the calcitonin receptor. Recept. Channels, 8 (3-4), 243–55.

7.     Woodrow JP, Sharpe CJ, Fudge NJ, Hoff AO, Gagel RF, Kovacs CS (2006). Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation. Endocrinology, 147(9), 4010-21.

8.     BalcI C, Sungurtekin H, Gürses E, Sungurtekin U, Kaptanoglu B (2003). Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit. Crit Care, 7 (1), 85–90