What does the Calcitonin Receptor do? — ASN Events

What does the Calcitonin Receptor do? (#126)

Rachel A Davey 1
  1. University of Melbourne, Heidelberg, Vic, Australia

Calcitonin acting via the calcitonin receptor (CTR), is a potent inhibitor of osteoclasts, the bone resorbing cells. Accordingly, calcitonin has been used to treat disorders characterised by increased bone resorption, including Paget’s disease and hypercalcaemia. The lack of any obvious pathophysiology in individuals either deficient in, or with excess levels of serum calcitonin, however, has led to much debate as to whether calcitonin, and/or the CTR, have a physiological role. Recent advances in the study of calcitonin and the CTR have been made using genetically modified mouse models, providing evidence for a physiological role of calcitonin and the CTR in regulating bone formation and in protecting the skeleton in times of calcium stress. Global knockout mouse models for either calcitonin and its related peptide (CGRP) or the CTR have identified a surprising physiological role for calcitonin and the CTR in inhibiting bone formation. CT/CGRP KO and global-CTRKO mice have increased bone mass due to increased bone formation. The inhibitory action of the CTR does not appear to be mediated via its expression on osteoclasts as osteoclast-specific CTRKOs have normal bone mass. The mechanism by which the CTR exerts its inhibitory effects on bone formation remains to be elucidated, but may be via it actions on osteocytes and/or the central nervous system. Further evidence from these CT/CGRP and CTRKO mouse models also suggest that calcitonin, acting via the CTR, plays an important role in regulating and conserving bone during times of increased bone resorption such as in calcitriol induced-hypercalcemia, and in high states of calcium demand, such as pregnancy and lactation. Studies utilising global and tissue-specific knockout mouse models of calcitonin or the CTR are continuing to provide further insight into the physiological role of calcitonin and its receptor in regulating bone and calcium homeostasis.