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Departments of Pathobiology and Laboratory Medicine, University of Toronto and Mount Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada
2To whom correspondence should be addressed.
We examined how cholecalciferol (vitamin D) nutrition affected serum
25-hydroxycholecalciferol (25(OH)D) and 1,25-dihydroxycholecalciferol
(1,25(OH)2D). Rats were fed conventional diet (vitamin D,
4.5 IU/g, or 7 nmol/d) or the same diet plus 18 nmol/d of
extra vitamin D for 3 wk. The extra vitamin D resulted in greater serum
25(OH)D (51 ± 3, vs. control of 21 ± 2 nmol/L), and
kidney mRNA for vitamin D receptor [VDR mRNA] (P
= 0.026) and lower serum 1,25(OH)2D (72 ± 16 vs.
control of 161 ± 10 pmol/L, P = 0.001), and
parathyroid hormone (PTH) (89 ± 4 vs. control of 160 ± 15
ng/L, P = 0.001). Kidney VDR mRNA relative to GAPDH
mRNA correlated inversely with serum 1,25(OH)2D
(r = -0.714, P = 0.006). There
were no differences in serum calcium, phosphate, alkaline phosphatase,
or weight gain. Experiment 2 compared groups supplemented with 0.2, 2
or 20 nmol/d of vitamin D orally, or 20 nmol/d dermally to see how
vitamin D nutrition influenced the response of 1,25(OH)2D
to changes in diet calcium. Vitamin D did not affect urinary calcium or
pyridinoline excretion, serum calcium, phosphate, vitamin D binding
protein or alkaline phosphatase. In groups given 20 nmol/d of vitamin
D, renal mitochondrial 25(OH)D-1
-hydroxylase was lower
(P < 0.01) and 25(OH)D-24-hydroxylase was higher
(P < 0.05). Higher 25(OH)D concentration was
related to proportionally lower 1,25(OH)2D at every calcium
intake, indicating greater tissue sensitivity to
1,25(OH)2D. We conclude suppression of
1,25(OH)2D and PTH, and higher renal VDR mRNA and
24-hydroxylase did not involve higher free 1,25(OH)2D
concentration or a first pass effect at the gut. Thus, 25(OH)D or a
metabolite other than 1,25(OH)2D is a physiological,
transcriptionally and biochemically active, noncalcemic vitamin D
metabolite.
KEY WORDS: vitamin D calcium adaptation parathyroid hormone rats transcription
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