Calcitonin

Calcitonin, which is also known as thyrocalcitonin, is a hormone made up of 32 amino acids. It is secreted by the parafollicular cells which are also known as C-cells that are present in the thyroid glands in humans. In other animals, the calcitonin hormone is produced by the C-cells in the ultimopharyngeal body. The main calcitonin function is to reduce the blood calcium (Ca2+) which is acting opposite to the function of the parathyroid hormone. Calcitonin hormone is also found in fish, reptiles, birds, and mammals. These proteins belong to the calcitonin-like protein family. 

Discovery and Identification of Calcitonin Hormone Function

Douglas Harold Copp and B.Cheney discovered a peptide hormone in 1962, which they found to be “maintaining normal calcium tone” i.e. maintaining an appropriate concentration of calcium in the serum. They first thought that the hormone was produced by the parathyroid gland in the human body, but researchers Ian Macintyre and his team, later showed that this hormone thyrocalcitonin/calcitonin hormone was actually produced by the parafollicular cells that are present in the thyroid gland of the human body. 

Thyrocalcitonin/Calcitonin Structure

The structure of any protein or polypeptide plays a significant role in its function such as the role of calcitonin structure in the calcitonin action of maintaining serum calcium levels by lowering them acting against the function of parathyroid hormone. An image given below shows the structure of the calcitonin hormone:

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As can be observed from the image, calcitonin is made up of a single alpha-helix chain of 32 amino acids, weighing 3454.93 daltons. Sometimes because of the alternative splicing of the gene CALC 1, responsible for coding of calcitonin protein, leads to the production or secretion of a 37 amino acid polypeptide known as calcitonin gene-related peptide, beta type. This distantly related hormone performs the similar function of maintaining calcium levels in the serum-like calcitonin. Although in humans, the role of calcitonin as a significant regulator of calcium levels isn't well established, it is shown in other animals like salmon to play an important role in lowering the calcium levels in the serum or plasma. Therefore, in certain disease conditions such as hypercalcemia, salmon calcitonin is used as a nasal spray to regulate calcium levels in humans. There exists approximately 50% similarity between the amino acids sequences of the salmon and human calcitonin. 

Secretion of Calcitonin and Its Regulation

Calcitonin definition clearly states that the calcitonin hormone is a peptide that is formed by the larger prepropeptide which is the product of the CALC 1 gene. This gene belongs to a superfamily of protein hormones that also includes other hormones such as islet amyloid precursor protein, calcitonin gene-related peptide and the precursor of adrenomedullin. The main calcitonin function is opposing the effect of parathyroid hormone and Vitamin D3. 

There are two main factors that lead to the secretion or release of calcitonin/thyrocalcitonin. They are:

• Increase in the calcium ion levels in the serum or the plasma. 

• when stimulated by the gastrin hormone (a peptide hormone known to stimulate gastric acids) or pentagastrin (a synthetic peptide hormone that performs the same function although structurally different with respect to pentagastrin.)

Uses of Calcitonin

Calcitonin finds a variety of applications in the fields of biological sciences and the pharmaceutical industry. It can be used in labs for experiments and also counteract certain disease conditions that are medically recognised. Some of the application and uses of calcitonin are given below:

• In the field of molecular biology, the gene responsible for the coding of calcitonin was the first gene in mammalian cells that was known for undergoing alternative splicing. Now, this mechanism has been well established and is found as a ubiquitous mechanism in all eukaryotes. 

• A calcitonin assay has been developed that is used for the identification of nodular thyroid diseases, and early diagnosis of medullary carcinoma (medullary thyroid cancer) that occurs due to the malignancy of parafollicular cells leading to an increase in the serum calcitonin level. 

• It is used as a tumour marker for medullary thyroid cancer. Increased levels of calcitonin have also been reported in many cases such as acute kidney injury, chronic kidney failure, hypergastrinemia and other gastrointestinal disorders and pulmonary diseases. 

• The most prominent use of calcitonin has been in the treatment of hypercalcemia or osteoporosis, a condition which is characterised by low bone mass, micro-architectural disorientation of the bone tissue, and bone fragility caused by the disorientation leading to an increase in the risk of fracture, especially in the elderly.

• A recent study has also shown that the use of calcitonin helps restore or increase bone mass especially in women with type 2 diabetes that gives rise to complications along with osteoporosis resulting in reduced fracture risk and any such incidence of bone damage. An image given below shows calcitonin action on the spine.
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• There are very few studies that have been performed using calcitonin that describe a potential for calcitonin function to lead to the treatment of bipolar study. Although promising, no further research has been done in this regard and significant study is lacking in this direction. 

• In the pharmaceutical industry, salmon calcitonin is produced by either recombinant DNA technology or chemical peptide synthesis for the treatment of hypercalcemia or osteoporosis. It has been found that although there are some differences between the salmon and human calcitonin, salmon calcitonin is much more active than the human counterpart. Hence, salmon calcitonin is used in a number of treatments of conditions like postmenopausal osteoporosis, Paget’s disease, bone metastasis and phantom limb pain. Also, the use of salmon calcitonin is found to be more appropriate for humans because of its rapid absorption and subsequent elimination by the body. But some researchers have shown to maintain caution as the salmon calcitonin can incite an antibody response. 

Thus, although not playing a significant role in serum calcium regulation in the human body, calcitonin has been shown to be quite effective for treatments of diseases related to the bone and the detection of cancer relating to the parafollicular cells.