Action of Thyrocalcitonin

Little or no change has been observed in the plasma magnesium con- 

Gudmundsson et al. (G4) found that thyrocalcitonin produced no fall in calcium in parathyroidectomized rats, although the hypophosphatemic response was still present. If, however, the parathyroidectomized rats were previously fed a diet high in calcium and low in phosphate, so that 

The effect on systemic plasma calcium concentration of a 1-hour iv infusion of calcium gluconate, before and after thyroidectomy, in normal and methyl-thiouracil-treated pigs of similar age and weight. The shaded areas represent the periods of infusion (14 mg of Ca/kg of body weight/hour). [Redrawn from Duncan and Care (Dl).] 

Stahl et al. (S3) have recently reported that injection of thyrocalcitonin after thyroparathyroidectomy results in a fall in the plasma 

Effect on plasma calcium concentration of a single injection of porcine thyrocalcitonin into an intact pig. 

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The kidney is obviously a possible site of action of thyrocalcitonin increased output of calcium in the urine might well account for the rapid fall in plasma calcium levels. Kenny and Heiskell (Kl), however, found that thyrocalcitonin produced an increased excretion of phosphate in the rat, but no significant effect on urinary calcium or creatinine output. Milhaud and Moukhtar (M9) obtained similar results in thyro-parathyroidectomized rats, although Stahl et al. (S3) found that the increased ratio of phosphate to creatinine in the urine of intact animals treated with thyrocalcitonin did not occur if there had been prior thyro-parathyroidectomy. 

The actions of thyrocalcitonin on the alimentary tract do not appear to be of major significance. Aliapoulios and Munson (Al) found that administration of the hormone to rats produced the expected hypocalcemia, even when the entire gastrointestinal tract had been removed. Clearly, changes in calcium absorption or fecal loss cannot be relevant to the immediate drop in plasma calcium level. However, previous fasting, or the administration of a low-calcium diet for some days, appears to sensitize the rat to the effects of thyrocalcitonin (H4, Kl). 

Significant differences in the apparent secretion of thyrocalcitonin might of course result from differences in the rate of destruction of the hormone, rather than from differences in its rate of secretion. A heat-labile factor that inactivates thyrocalcitonin has been found in plasma (T4), but its part in controlling the action of the hormone is as yet uncertain. 

The known effects of thyrocalcitonin are primarily in bone. Removal of the gut had no effect on the hypocalcemic effect of calcitonin (A6), and neither did nephrectomy (H8). No change in soft tissue calcium content was seen in soft tissues to explain the hypocalcemia (Kl). Calcitonin apparently inhibits bone resorption and thereby decreases calcium entry into the blood. Calcitonin prevents the release of calcium from cultured bone (A5, FIO). In vivo, the release of Ca from prelabeled bone is decreased by calcitonin (Jl). The bone arteriovenous difference in calcium levels is increased by calcitonin (M3). The mode of action of calcitonin is unknown. Calcitonin does not inhibit parathormone (A6, H7, T3), nor is its effect apparently mediated through RNA synthesis (T3). 

Elucidation of thyrocalcitonin s mechanism of action hopefully may provide new clues on the pathogenesis of osteoporosis (lack of hormone) and such diseases as Albers-Sch5nberg disease (osteopetrosis marble disease). 

In summary, therefore, thyrocalcitonin action on bone appears to be more in the nature of an inhibition of the uptake of bone calcium and phosphorus into the extracellular fluid, rather than an accelerated deposition of these elements. Further careful in vitro and in vivo studies will probably be necessary before the nature of the relationship between thyrocalcitonin action and parathormone action is clarified. 

Several animal species have been used in the biological assay of calcium-lowering hormones. For reasons of size, the rat is most commonly used, although mice have been claimed to be more responsive to human thyrocalcitonin preparations (S2). For studies of the course of thyro-calcitonin action in which serial blood samples were required, both pigs (C5) and goats (F4) have been used. For assessment of the potency of hoimone preparations, bioassay in rats is in general satisfactory. 

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