Molecular physiology and pharmacology of calcitonin.

Calcitonin is a thirty-two amino acid peptide that contains an N-terminal disulphide bridge and a C-terminal prolineamide residue. It is released from thyroid parafollicular C-cells and its direct actions on the osteoclast account for its physiological effects whether as a hypocalcaemic agent and a potent inhibitor of bone resorption. These effects likely reflect actions upon a number of specific osteoclast cell surface receptors that initiate intracellular signaling events through both cyclic AMP and calcium mediated second messenger pathways. Studies of its potent anti-resorptive effects have significant translational implications in the management of Paget's bone disease, osteoporosis, and hypercalcaemia. This chapter summarizes major concepts in the synthesis and structure of calcitonin and then proceeds to outline its cellular, molecular actions and therapeutic applications, whilst seeking to provide a reference source. More detailed accounts have been given on different aspects of calcitonin physiology and biochemistry in a number of recent reviews by ourselves and others (155,157, Zaidi et al., 1994; 2002).