Calcitonin Totally Explained

Everything about Calcitonin totally explained

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Calcitonin is a 32-amino acid polypeptide hormone that's 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)
It has been found in fish, reptiles, birds, and mammals. Its importance in humans hasn't 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 . 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: ť :- Prevent postprandial hypercalcemia resulting from absorption of Ca²⁺ from foods during a meal

:- Promote mineralization of skeletal bone ť :- Protect against Ca²⁺ loss from skeleton during periods of Ca²⁺ stress such as pregnancy and lactation

Vitamin D regulation

A satiety hormone: ť :- 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 isn't 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 doesn't 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's 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.

Further Information

Get more info on 'Calcitonin'.

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