VIVO Pathophysiology
Calcitonin
Calcitonin is a hormone known to participate in calcium and phosphorus metabolism. In mammals, the major source of calcitonin is from the parafollicular or C cells in the thyroid gland, but it is also synthesized in a wide variety of other tissues, including the lung and intestinal tract. In birds, fish and amphibians, calcitonin is secreted from the ultimobrachial glands.
Calcitonin is a 32 amino acid peptide cleaved from a larger prohormone. It contains a single disulfide bond, which causes the amino terminus to assume the shape of a ring. Alternative splicing of the calcitonin pre-mRNA can yield a mRNA encoding calcitonin gene-related peptide; that peptide appears to function in the nervous and vascular systems. The calcitonin receptor has been cloned and shown to be a member of the seven-transmembrane, G protein-coupled receptor family.
Physiologic Effects of Calcitonin
A large and diverse set of effects has been attributed to calcitonin, but in many cases, these were seen in response to pharmacologic doses of the hormone, and their physiologic relevance is suspect. It seems clear however, that calcitonin plays a role in calcium and phosphorus metabolism. In particular, calcitonin has the ability to decrease blood calcium levels at least in part by effects on two well-studied target organs:
- Bone: Calcitonin suppresses resorption of bone by inhibiting the activity of osteoclasts, a cell type that "digests" bone matrix, releasing calcium and phosphorus into blood.
- Kidney: Calcium and phosphorus are prevented from being lost in urine by reabsorption in the kidney tubules. Calcitonin inhibits tubular reabsorption of these two ions, leading to increased rates of their loss in urine.
It seems clear that there are species differences in the importance of calcitonin as a factor affecting calcium homeostasis. In fish, rodents and some domestic animals, calcitonin appears to play a significant role in calcium homeostais. In humans, calcitonin has at best a minor role in regulating blood concentrations of calcium. One interesting piece of evidence to support this statement is that humans with chronically increased (medullary thyroid cancer) or decreased (surgical removal of the thyroid gland) levels of calcitonin in blood usually do not show alterations from normal in serum calcium concentration.
Addition information on calcitonin and calcium balance can be found in the section Endocrine Control of Calcium and Phosphate Homeostasis.
Control of Calcitonin Secretion
The most prominent factor controlling calcitonin secretion is the extracellular concentration of ionized calcium. Elevated blood calcium levels strongly stimulate calcitonin secretion, and secretion is suppressed when calcium concentration falls below normal. A number of other hormones have been shown to stimulate calcitonin release in certain situations, and nervous controls also have been demonstrated.
Disease States
A large number of diseases are associated with abnormally increased or decreased levels of calcitonin, but pathologic effects of abnormal calcitonin secretion per se are not generally recognized.
There are several therapeutic uses for calcitonin. It is used to treat hypercalcemia resulting from a number of causes, and has been a valuable therapy for Paget disease, which is a disorder in bone remodeling. Calcitonin also appears to be a valuable aid in the management of certain types of osteoporosis.
Advanced and Supplemental Topics
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