1,25(OH)2D response to combined zinc and phosphorus depletion in rats

To investigate the role of zinc depletion in the response of calcitriol to a single provocative stimulus, we studied vitamin D metabolites, parathyroid hormone (PTH), and mineral balance during phosphorus depletion in animals with different zinc nutritional status. Male Lewis rats (66) were pair fed normal phosphorus (NP), zinc-replete (+) or -deplete (-) diets for 2 wk. Thereafter, one-half of each paired group underwent 1 wk of phosphorus depletion (LP). Zinc-deplete animals had lower plasma zinc, and phosphorus-deplete animals had lower plasma phosphorus concentrations than respective nutritionally replete controls. Plasma calcium, PTH, and 25-hydroxycholecalciferol concentrations were similar in all four groups at end of experiment. Mean plasma 1,25(OH)2D concentration increased 80% from 35 +/- 3 to 63 +/- 9 pg/ml (P less than 0.007) when values were compared before and after phosphorus restriction in zinc-replete animals (LP + group). The 7.9% increase from 35 +/- 4 to 38 +/- 4 pg/ml in 1,25(OH)2D concentration in animals with combined zinc and phosphorus depletion (LP-) was not significant. External calcium balance, however, was maintained in the combined zinc and phosphorus-deplete group. We conclude that zinc depletion limits the increase in plasma 1,25(OH)2D concentration associated with phosphorus depletion. The mechanism is unknown but may involve an effect of zinc on renal 25(OH)D 1-alpha-hydroxylase synthetic activity.