To test the hypothesis that in the
vitamin D-deficient state the activity of 25-hydroxyvitamin D3-1 alpha-
hydroxylase (25-OHD3-1 alpha-hydroxylase) is modulated by
parathyroid hormone and the plasma concentration of
phosphate only in the presence of small amounts of
1,25-dihydroxyvitamin D3 (or some other metabolite of
vitamin D), we measured the activity of this
enzyme 24 h after
parathyroidectomy (PTX) in frankly hypocalcemic,
vitamin D-deficient chicks that were not supplemented with
vitamin D or one of its metabolites. The otherwise predictable complications of PTX in this metabolic setting (
hypocalcemia of increasing severity,
tetany, moribundity, and death) were prevented by continuous
intravenous administration of
calcium (as a
solution of
calcium chloride/
calcium gluconate 1:1) through a
catheter in the external jugular vein placed at the time of PTX. The findings were as follows: (a) The activity of 25-OHD3-1 alpha-
hydroxylase was significantly less in the parathyroidectomized group than in the
sham-operated control chicks (P less than 0.001). (b) The reductive effect of PTX on the activity of this
enzyme was significantly attenuated when
hypophosphatemia was increased in severity by administration of
glucose. (c) In the post-PTX state the activity of 25-OHD3-1 alpha-
hydroxylase and plasma concentration of
phosphate were significantly, inversely related (P less than 0.001). (d) In the
sham-operated control group the activity of this
enzyme and the plasma concentration of
phosphate were not significantly correlated. These findings indicate that in the
vitamin D-deficient state, both circulating
parathyroid hormone and the plasma concentration of
phosphate can significantly modulate the activity of 25-OHD3-1 alpha-
hydroxylase in the absence of
vitamin D or its metabolites. The findings also suggest that in the
vitamin D-deficient state the plasma concentration of
phosphate modulates the activity of this
enzyme only when the concentration of circulating
parathyroid hormone is not increased.