Calcitonin

CALCITONIN

Calcitonin release is normally stimulated by rising serum calcium levels and suppressed by hypocalcemia. The major physiological effects of calcitonin are inhibi-tion of bone resorption and deposition of postabsorp-tive calcium into bone following a meal, which prevents postprandial hypercalcemia.

Chemistry

Calcitonin is a single-chain polypeptide composed of 32 amino acid residues having a molecular weight of ap-proximately 3600. A cysteine disulfide bridge at the 1-7 position of the amino terminal end of the peptide is es-sential for biological activity; however, the entire amino acid sequence is required for optimal activity.

Synthesis and Secretion

The regulation of calcitonin synthesis and release from the parafollicular C cells of the thyroid gland is cal-cium dependent. Rising serum calcium is the principal stimulus responsible for calcitonin synthesis and re-lease. Other hormones, such as glucagon, gastrin, and serotonin, also stimulate calcitonin release. Calcitonin has been isolated in tissues other than the parafollicu-lar C cells (parathyroid, pancreas, thymus, adrenal), but it is not known whether this material is biologically active.

Secretagogues, such as gastrin and pancreozymin, may contribute significantly to the regulation of en-dogenous calcitonin. In fact, it has been postulated that gastrin-induced calcitonin release following meals may help regulate the postprandial calcium deposition in bone.

A calcitonin precursor has been identified within the thyroid parafollicular C cells. It is thought to function in a manner analogous to that of proPTH to facilitate in-tracellular transport and secretion of the hormone. The metabolic degradation of calcitonin appears to occur in both the liver and kidney.

Although blood calcitonin levels are normally low, excessive levels have been found in association with medullary carcinoma of the thyroid and more rarely carcinoid tumors of the bronchus and stomach. Serum calcitonin levels are used to screen and monitor patients who have or are suspected of having medullary carci-noma of the thyroid.

Mechanism of Action

Calcitonin interacts with specific plasma membrane re-ceptors within target organs to initiate biological ef-fects. This interaction has been directly linked to the generation of cAMP via adenylyl cyclase activation.