Calcitonin

The peptide calcitonin (CT) was initially discovered in 1962 as a novel hyp ocalcemic hormone. This hypocalcemic response was principally due to a pote nt inhibitory action of CT on osteoclast mediated bone resorption and it is this action which underlies its widespread clinical use for the treatment of bone disorders, including Paget's disease, osteoporosis and hypercalcemi a of malignancy. In this article we review the basic physiology of CT actio n, structure-function studies on CT peptides, cloning of CT receptors and t he identification of isoforms of the receptor derived from alterative splic ing of the receptor mRNA. We also review the state of understanding on CT r eceptor mediated signaling and receptor regulation, along with developing c oncepts of how CT peptides interact with the receptor, including how the re ceptors may interact with receptor activity modifying proteins to produce n ovel phenotypes. Finally, current therapeutic use is reviewed, and the pote ntial for expanded use that may come with advances in delivery of peptides or CT mimetics.