242 H. A. SoLiMAN et al.: Mode of Action of Calcitonin 



Mode of Action of Calcitonin 



H. A. SoLiMAN '■'", C. J. Robinson, G. V. Foster, I. MacIntyre 



Department of Chemical Pathology, Postgraduate Medical School, Ducane Road, London, 



England 



In our laboratory perfusion studies in the dog and goat have demonstrated the 

 secretion of calcitonin by the thyroid gland. Our findings in the dog have been 

 confirmed by Bernstein et al. (1965). We present here studies of the mode of action 

 of the new hormone. 



Acetone-dried pig thyroid was extracted with hot hydrochloric acid, dialysed, 

 fractionated with NaCl and the active precipitate dissolved in acetate buffer. This 

 salt precipitated fraction was used in these studies. A single intravenous dose of 

 calcitonin in the rat produced a prompt fall in plasma calcium and phosphate. The 

 possibility of the existence of plasma calcium lowering principles in other tissue 

 extracts was examined. Beef parathyroid, pig liver and ox kidney were dealt with in 

 a similar manner to the thyroid tissue. Equal doses, on the basis of protein nitrogen 

 content of these extracts, and one-tenth of this dose of thyroid extract were tested in 

 the rat. Extracts from the other tissues produced a small, non-specific fall in plasma 

 calcium, compared to the marked drop produced by the thyroid extract. 



In vitamin D-induced hypercalcemia and hyperphosphataemia in the rat, the 

 hormone was found to be still potent in lowering both plasma calcium and phos- 

 phate. Calcitonin was also active in calcium deficient and in magnesium deficient 

 rats. The hormone lowered the plasma calcium in vitamin D deficient rats, and there- 

 fore its activity is not dependent on vitamin D. 



Removal of the kidneys did not alter the plasma calcium-lowering response to the 

 calcitonin injection and, therefore, this effect is not mediated via a renal mechanism. 

 The plasma calcium lowering effect was not accompanied by an Increase in soft tissue 

 calcium. 



These two facts, that the calcium lowering activity Is not mediated through a 

 renal mechanism and is not accompanied by an increase in soft tissue calcium, point 

 strongly to the bone as the site of action of calcitonin. 



A new concept of the mode of action of hormones is that they may act by control 

 of gene activity. The possibility of a genotropic action for calcitonin was investi- 

 gated. The antibiotic, actlnomycin D is a specific inhibitor of DNA-dependent synthe- 

 sis of RNA. Actlnomycin injected three hours prior to calcitonin did not block Its 

 action. 



The conclusion is that concurrent synthesis of RNA is not necessary for calcitonin 

 to exert its two cardinal acute actions on plasma calcium and phosphate. This is 

 analogous to the rapid glucose lowering action of insulin, which cannot be blocked by 

 actlnomycin D. 



In parathyroidectomlsed rats calcitonin produced a marked drop in the plasma 

 phosphate, without an appreciable effect on plasma calcium. However, in para- 

 thyroidectomlsed rats fed a high calcium, low phosphate diet, the hormone lowered 

 both plasma calcium and phosphate. 



* United Arab Republic Sdiolar. 



