Hypocalcemic effect of elcatonin in mouse models for humoral hypercalcemia of malignancy

Abstract

To elucidate the effect of calcitonin on humoral hypercalcemia of malignancy (HHM), we studied the effect of elcatonin, a synthetic eel calcitonin analog, on plasma calcium concentration in hypercalcemic nude mice transplanted subcutaneously with FA-6 pancreas cancer cells and hypercalcemic mice produced by continuous infusion of parathyroid hormone-related peptide (PTHrP). Elcatonin proved to exert a potent hypocalcemic effect in either model for hypercalcemia. The effect reached peaks at 2 hr after its administration, and it was no longer detected at 24 hr. The dose-dependent effects of a single administration of elcatonin were studied in the FA-6 tumor-bearing mice: the hypocalcemic effect of elcatonin at 1-2 hr after administration was dose-relatedly augmented. The effect of daily administration of elcatonin was further studied in the FA-6 tumor-bearing mice: 5-Day daily administration of elcatonin was not accompanied by reduction in its hypocalcemic effect. Moreover, it was suggested that higher the efficacy of elcatonin, the higher were the plasma calcium concentrations in the tumor-bearing mice. These results indicated that elcatonin exerts an immediate hypocalcemic effect even on models for acute and severe hypercalcemia such as FA-6 tumor-bearing mice, that this hypocalcemic effect became more potent depending on their elevation of plasma calcium concentration, and that elcatonin exerts a hypocalcemic effect even on a model for hypercalcemia due to PTHrP, a presumable causative substance of HHM.