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High Yield Notes
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Content Reviewers:

Rishi Desai, MD, MPH

The body’s blood calcium level stays stable thanks to three hormones: parathyroid hormone, vitamin D, and calcitonin.

Parathyroid hormone and vitamin D help increase calcium levels, whereas calcitonin helps lower them. Let’s focus on the role of calcitonin.

The majority of the extracellular calcium, the calcium in the blood and interstitium, is split almost equally into calcium that’s diffusible and calcium that’s not diffusible.

Diffusible calcium is small enough to diffuse across cell membranes and there are two subcategories.

The first is free-ionized calcium, which is involved in all sorts of cellular processes like neuronal action potentials, contraction of skeletal, smooth, and cardiac muscle, hormone secretion, and blood coagulation, all of which are tightly regulated by enzymes and hormones.

The second category is complexed calcium, which is where the positively charged calcium is ionically linked to tiny negatively charged molecules like oxalate and phosphate, which are small anions, that are found in our blood.

The complexed calcium forms a molecule that’s electrically neutral but unlike free-ionized calcium it’s not useful for cellular processes.

Finally there’s the non-diffusible calcium which is bound to large negatively charged proteins like albumin.

The resulting protein-calcium complex is too large and charged to cross membranes, so the non-diffusible calcium is also uninvolved in cellular processes.

Now, calcitonin is a polypeptide hormone involved in regulating blood calcium levels.

Calcitonin comes from the parafollicular cells, or C cells, of the thyroid gland which is a gland located in the neck that looks like two thumbs hooked together in the shape of a “V”.

The thyroid gland is made up of thousands of follicles, which are small spheres lined with follicular cells.

C cells are adjacent to follicles, more precisely in the connective tissue that separates the follicles.

C cells synthesize preprocalcitonin, a peptide with 141 amino acids, which becomes procalcitonin after a signal peptide is cut off by an enzyme via proteolytic cleavage, leaving 116 amino acids.

From there, procalcitonin is cleaved again into the 33 amino acid-long immature calcitonin, and finally cleaved one more time into mature calcitonin, which has 32 amino acids.

It’s then stored in secretory granules in C cells, waiting to be released.

Normally total blood calcium is between 8.5 to 10 mg/dl.

And changes in calcium levels are detected by a calcium-sensing surface receptor on C cells.


Calcitonin is a polypeptide hormone that regulates calcium levels in the blood. It is secreted by the parafollicular cells (C cells) of the thyroid gland in response to elevated serum calcium levels. Calcitonin lowers serum calcium by inhibiting calcium release from bone marrow and slowing down the absorption of dietary calcium.

Calcitonin plays a crucial role in maintaining calcium homeostasis; thus, its blood levels are tightly regulated. Elevated calcitonin levels are seen in conditions such as hyperthyroidism and thyroid malignancy.

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  2. "Physiology" Elsevier (2017)
  3. "Human Anatomy & Physiology" Pearson (2018)
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  6. "Calcitonin Receptor Plays a Physiological Role to Protect Against Hypercalcemia in Mice" Journal of Bone and Mineral Research (2008)