Parathyroid function and magnesium depletion in the rat.

Hypocalcemia is characteristically observed in magnesium deficiency in a number of animal species. Previous studies demonstrated impaired release of PTH in magnesium-depleted hypocalcemic humans. However, an enigma remains in that, unlike in other animals, hypercalcemia, rather than hypocalcemia, accompanies magnesium deficiency in the rat. Because intact parathyroids are necessary for the development of this hypercalcemia, it has been postulated that magnesium depletion stimulates, rather than impairs, PTH secretion in the rat. In an effort to more directly evaluate this thesis, sequential measurements of circulating immunoreactive PTH (iPTH) were made over a 30-day period in rats maintained on a magnesium-deficient diet and in match-fed controls. In the control rats, serum calcium, magnesium, and iPTH remained relatively constant throughout the study. By contrast, during the first 4 days of a low magnesium diet, serum magnesium decreased to 1.0 mg/dl, serum calcium increased moderately, while serum iPTH increased to a mean level that was twice that in controls. After 5 days, when serum magnesium progressively fell to levels less than 0.6 mg/dl and serum calcium continued to rise, serum iPTH fell to levels significantly lower than the control value. In a second set of experiments, the effect of hypocalcemia on circulating iPTH in magnesium deficiency was evaluated. Circulating iPTH was greatly increased and not significantly different in magnesium-deficient and magnesium-replete animals who were rendered chronically hypocalcemic by diets deficient in either calcium or vitamin D. The results of this study indicate that: 1) in the rat, an increase in PTH secretion occurs early in the genesis of magnesium deficiency in the presence of a modest increase in serum calcium; however, the subsequent further increase in serum calcium counteracts the stimulatory effect of hypomagnesemia on PTH secretion; 2) unlike the human parathyroid gland, the rat parathyroid gland responds appropriately to both hypo- and hypercalcemia in magnesium deficiency; and 3) the hypercalcemia that occurs in the magnesium-deficient rat is not due to increased PTH secretion and must be accounted for by another mechanism.