Sigmoidal relationship between calcitonin and calcium: Studies in normal, parathyroidectomized, and azotemic rats

Abstract

Calcitonin secretion is stimulated by acute hypercalcemia. Furthermore, in the rat, the calcemic response to parathyroid hormone (PTH) is decreased by calcitonin stimulation. However, in renal failure, it is not known if an increase in the serum calcium concentration within the physiologic range of serum calcium stimulates calcitonin and whether the increased calcitonin decreases the calcemic response to PTH. In the present study, four groups of pair-fed rats were evaluated: normals (N); parathyroidectomy (PTX); and two groups with renal failure (RF) - basal serum calcium < 8.5 mg/dl (RF(a)) and basal serum calcium > 8.5 mg/dl (RF(b)). was induced by parathyroidectomy or in the RF(a) group, by a high phosphate diet. Increases in the serum calcium were produced by a 48 hour infusion of rat 1-34 PTH. In the RF(a) and PTX groups, stimulation of calcitonin was observed as the serum calcium increased from hypocalcemia to normal levels of calcium (P < 0.01). In all four groups, increasing the serum calcium from normal levels to hypercalcemia increased the serum calcitonin level (P < 0.05). The relationship between serum calcitonin and calcium was best expressed as a sigmoidal curve. In the two groups with basal hypocalcemia, PTX and RF(a), the calcitonin-calcium curve was shifted to the left of the N and RF(b) groups. In conclusion, 1) the presence of a calcitonin-calcium curve suggests the possibility of a regulatory function for calcitonin during acute increases in the serum calcium; 2) the basal serum calcium concentration may determine the calcium level at which calcitonin is stimulated; and 3) the stimulation of calcitonin in the physiologic range of serum calcium suggests that endogenous calcitonin production may decrease the calcemic response to PTH in renal failure.