Calcium Regulatory Action of Endogenous Rat Calcitonin Demonstrated by Passive Immunization with Calcitonin Antibodies*

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Abstract
The calcium regulatory role of calcitonin (CT) in murine physiology was evaluated with a combination of immunological techniques, bioassays, and gland ablation. Passive immunization of rats with neutralizing CT antibodies caused an immediate but transient increase in plasma calcium with a time course similar to that observed in thyroparathyroidectomized animals. In animals fasted during the day and fed at night (1700– 0700 h), acutely decreasing endogenous CT (<100 pg/ml) by thyroparathyroidectomy or by passive immunization with CT antibodies resulted in a greater increase in plasma calcium in the preprandial (1600 h) than in the postprandial (1000 h) period. Data pooled from these periods revealed a paradoxical inverse correlation between immunoreactive CT and plasma calcium, a known secretagogue for CT. In these animals on a restricted feeding schedule, a sharp preprandial (1600 h) rise in immunoreactive and bioactive CT and a circadian rhythm in plasma calcium were also observed. The onset of the increase in circulating CT preceded the onset of feeding and coincided with or shortly preceded the daily nadir of plasma calcium. These findings establish that CT has a primary calcium regulatory role in murine physiology. More specifically, they demonstrate that 1) the postthyroparathyroidectomy increase in plasma calcium is due specifically to the loss of CT, 2) passive immunization is a feasible technique for evaluating the actions of endogenous CT, 3) the role of CT in calcium regulation cannot be restricted to that of preventing prandial and postprandial increase in blood calcium, and 4) factors other than calcium must be involved in the control of CT secretion in the nonfed state.