Calcitonin

Definitions & Key takeaways

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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Introduction0:00–0:19

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.

Calcium Regulation0:19–1:33

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”.

Synthesis1:33–2:32

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.

Control2:32–2:51

And changes in calcium levels are detected by a calcium-sensing surface receptor on C cells. If the concentration of calcium in the blood goes above the normal range, C cells release calcitonin, lowering blood calcium levels.

Functions2:51–5:01

What makes calcitonin different from say, parathyroid hormone, in calcium homeostasis is that it’s not actually involved in minute-to-minute regulation of blood calcium concentration.
In fact, the exact role of calcitonin in the body is still a bit of a mystery, because if the body stops producing calcitonin - for example when the thyroid is surgically removed - the regulation of blood calcium doesn’t seem to be affected.
Weird, right? Still, we do know that the body responds to calcitonin and it’s sometimes used in high doses to treat hypercalcemia.
Calcitonin contributes to lowering blood calcium levels in two ways. First, its major action is in the bones, and second through minor effect in the kidneys.
In the bones, calcitonin binds to the calcitonin receptor on the basal surface of osteoclasts, which are bone eating cells.
Normally, osteoclasts attach to the bone matrix and its membrane forms many little arms called a ruffled border which helps them attach to the bone and increased the surface area through which they secrete acid that breaks down bone, also called bone resorption.
This releases the two minerals that make up bone - calcium and phosphate - into the blood. When calcitonin binds to its G protein coupled receptor on osteoclasts, a G protein is released inside the cell which activates adenylate cyclase.
This enzyme converts adenosine triphosphate or ATP into cyclic AMP or cAMP. Increased levels of cAMP causes the osteoclasts to decrease the number of arms formed by the membrane and they can’t maintain the ruffled border, leading to decreased bone resorption and decreased blood calcium concentration.
Second, calcitonin has a minor effect in the kidneys, more specifically the distal convoluted tubule, which also happen to have calcitonin receptors.
When it binds to the receptor, it decreases calcium and phosphate reabsorption by the principal cells of the distal convoluted tubules, which use Na+/Ca++ channels on their apical surface to return calcium from the urine back to the body.
So increased calcitonin leads to more calcium and phosphate being lost in the urine, also known as calciuria and phosphaturia.
Alright, as a quick recap, calcitonin is released when the calcium-sensing receptor on parafollicular, or C cells detect an increase in extracellular calcium.

Review5:01–5:25

It then works to inhibit bone resorption and causes phosphaturia and calciuria by the kidneys, decreasing the level of extracellular calcium.
These effects help keep total blood calcium levels between 8.5 to 10 mg/dl.