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.