Regulation of Calciotropic Hormonesin Vivoin the New Zealand White Rabbit*

Abstract

Serum levels of ionized calcium, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D[1,25-(OH)2D], intact immunoreactive PTH and calcitonin were measured in the laboratory rabbit to evaluate the role of these calciotropic hormones in calcium homeostasis in this species. We confirm the finding of previous researchers that the resting serum ionized and total calcium concentrations are elevated in rabbits compared to those in other species (ionized calcium, 1.70 +/- 0.13 mmol/liter; total calcium, 3.23 +/- 0.25 mmol/liter). The serum calcium concentrations in animals maintained on a breeding farm or in the laboratory did not differ significantly despite nearly 3-fold higher levels of vitamin D in the feed at the farm, which were associated with 3- to 4-fold higher concentrations of 25OHD and 1,25-(OH)2D. Baseline intact PTH levels for the farm and laboratory populations also did not differ significantly and averaged 69.4 +/- 43.6 human pgeq/ml (laboratory animals, 52.1 +/- 28.4; breeding farm animals, 86.0 +/- 49.5 human pgeq/ml). Infusions of calcium gluconate or EDTA for 15 min into anesthetized animals in the laboratory induced dramatic reciprocal changes in the measured circulating levels of PTH. Calcium gluconate infusions (190-300 nmol/g BW) produced 50-85% increases in serum ionized calcium, which were accompanied by 74-91% decreases in PTH levels (from 68.8 +/- 29.2 at time zero to 10.1 +/- 3.1 human pgeq/ml at 15 min) as well as 7-fold increases in calcitonin levels. EDTA infusions (14-120 nmol/g BW) reduced serum ionized calcium by 9-49%, while PTH levels increased by 68-560% (from 61.4 +/- 32.3 at time zero to a maximum of 138 +/- 48.6 human pgeq/ml at 3 min). During the EDTA infusion, the PTH response was variable after 3 min despite further decreases in ionized Ca2+, indicating either exhaustion of PTH reserves or regulation of the secretory response by some parameter other than ionized calcium concentration per se. Thus, the rabbit appears to defend its serum ionized calcium concentration against hypo- and hypercalcemia by rapid changes in PTH secretion and calcitonin. Unlike other mammalian species, however, the changes in PTH occur at relatively high levels of calcium, suggesting that the parathyroid gland of the rabbit is reset to respond to changes in ionized Ca2+ within the physiological range in that species. The relative insensitivity of the rabbit parathyroid to extracellular calcium is analogous to that observed in primary hyperparathyroidism and may be a useful model to study the control of normal and abnormal PTH secretion.