The dominant biological action of calcitonin is to mediate a lowering of serum calcium levels. Calcitonin is secreted in response to elevated blood levels of ionized calcium. Calcitonin is secreted by mammals, and fish and birds. The rate of calcitonin secretion is a direct function of the plasma calcium concentration (Figure 1). There is some evidence in rats and pigs that gastrin can function as a secretagogue for calcitonin secretion; however, there is no evidence of this response in humans.
Fig1. Changes in plasma levels of immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) as a function of plasma total calcium. The data were obtained in pigs given EDTA to decrease plasma calcium or given calcium infusions to increase plasma calcium. Note that, as serum calcium increases, iPTH falls and serum iCT increases; as serum calcium decreases the reverse occurs. Reproduced with permission of Arnaud, C. D. et al. (1970). In Calcitonin: Proceedings of the Second International Symposium (S. Taylor, ed.). Heinemann, London, p. 236.
In addition to the onset of hypocalcemia, there is also normally an accompanying hypophosphatemia after the administration of calcitonin. Also, in experimental animals, the blood level of calcitonin is elevated in pregnancy and lactation.
Three important biological functions for calcitonin have been proposed: (a) protection of the young ani mal or newborn against postprandial hypercalcemia; (b) blocking of the actions of PTH in mobilizing bone calcium and phosphorus; and (c) stimulation of the urinary excretion of both calcium and phosphate in the kidney. The net effect of these three actions is to mediate a reduction in serum calcium levels.
The biological effects of calcitonin are mediated as a consequence of the interaction of CT with its receptor present in the outer membrane of target cells of both skeletal and renal tissues and other target organs. The human calcitonin receptor has been cloned and sequenced and found to belong to the class II (family B) subclass of G-protein receptors. This receptor subfamily also includes PTH, PTHrP, secretin, and glucagon G-protein-coupled receptors with seven-transmembrane-spanning domains. The mature CT receptor comprises 490 amino acids. The activated CT receptor stimulates adenylate cyclase and production of cyclic AMP in many target organs including the kidney. However, in human osteoclasts, CT stimulates the activation of protein kinase C that mediates the known action of CT to inhibit osteoclast mediated bone resorption. The CT receptor is known to be expressed in kidney cells, osteoclasts, placenta, testis and spermatozoa, lung, and pituitary. The functional significance of these various isoforms of the calcitonin receptor remains to be established.
