Metabolism of 25-hydroxyvitamin D₃ in rats: Low-calcium diet vs. calcitriol infusion

It has been proposed that the decreased serum level of 25-hydroxyvitamin D [25(OH)D] observed with dietary Ca restriction is mediated by an increase in circulating 1,25-dihydroxyvitamin D [1,25(OH)₂D]. We compared the effects of endogenous and exogenous elevations in serum 1,25(OH)₂D on the production rate (PR), metabolic clearance rate (MCR), and excretory pathways of [³H]25(OH)D₃ in rats, with the use of steady-state techniques. Low-Ca diet and 1,25(OH)₂D₃ infusion caused comparable reductions in serum 25(OH)D and elevations in 1,25(OH)₂D. Low-Ca diet lowered serum 25(OH)D by increasing MCR from 21.8 ± 3.2 to 29.1 ± 5.4 (SD) μl·min^-1·kg^-1 (P ≤ 0.005) and decreasing PR from 944 ± 161 to 663 ± 163 pg·min^-1·kg^-1 (P ≤ 0.001). In contrast, 1,25(OH)₂D₃ infusion produced a dramatic rise in the MCR of 25(OH)D from 23.4 ± 4.5 to 62.8 ± 13.7 μl·min^-1·kg^-1 (P ≤ 0.001) and also increased the PR from 943 ± 165 to 1,500 ± 337 pg·min^{- 1}·kg^-1 (P ≤ 0.001). With 1,25(OH)₂D₃ infusion, urinary excretion of metabolites of [³H]25(OH)D₃ rose rapidly, and kidney homogenates from these rats demonstrated vigorous side-chain oxidation of [³H]-25(OH)D₃. With low- Ca diet, urinary tritium excretion increased more gradually, and no direct side-chain oxidation of [³H]25(OH)D₃ occurred in vitro. The increased MCR of 25(OH)D₃ with low-Ca diet could be accounted for by enhanced synthesis of 1,25(OH)₂D₃ and subsequent degradation in target tissues.