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 < 0.007) when values were compared before and after phosphorus restriction 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-α-hydroxylase synthetic activity.