Calcitonin: a review of its discovery and an account of purification and action.

Abstract

Plasma calcium is regulated with great precision: even large differences in diet change plasma calcium very little. McLean & Urist (1961) proposed that this constancy is achieved by appropriate alteration in the secretion rate of the parathyroid hormone. This hormone increases plasma calcium by increasing the rate of bone breakdown. Thus, a falling plasma calcium would stimulate the parathyroid glands to secrete more parathyroid hormone; a rising plasma calcium would produce inhibition of secretion. This hypothesis was first tested by Copp and colleagues in perfusion studies of the dog thyroid and parathyroid glands (Copp et al . 1962). Their results led them to postulate the existence of a new calcium-lowering hormone which they called calcitonin and which they thought came from the parathyroid glands. The existence of calcitonin was soon confirmed (Kumar, Foster & MacIntyre 1963). In experiments in the dog, the thyroid and parathyroid glands were perfused together in situ with blood of high and low calcium content. This was done without net addition or removal or calcium from the circulation (figures 20 and 21). There was a marked fall in systemic plasma calcium whenever the thyro-parathyroid glands were perfused with high-calcium blood (figure 22). This could have been due to inhibition of secretion of parathyroid hormone, but this explanation was excluded by control experiments. Complete removal of the thyroid and parathyroid glands produced little change in plasma calcium in the following two and a half hours (figure 23) in contrast to the marked hypocalcaemia accompanying thyro-parathyroid perfusion. Clearly a calcium-lowering substance was being liberated from the thyroid or parathyroid glands during high-calcium perfusion.