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 [H-3]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) mu-l.min-1.kg-1 (P less-than-or-equal-to 0.005) and decreasing PR from 944 +/- 161 to 663 +/- 163 pg.min-1.kg-1 (P less-than-or-equal-to 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-mu-l.min-1.kg-1 (P less-than-or-equal-to 0.001) and also increased the PR from 943 +/- 165 to 1,500 +/- 337 pg.min-1.kg-1 (P less-than-or-equal-to 0.001). With 1,25(OH)2D3 infusion, urinary excretion of metabolites of [H-3]25(OH)D3 rose rapidly, and kidney homogenates from these rats demonstrated vigorous side-chain oxidation of [H-3]- 25(OH)D3. With low-Ca diet, urinary tritium excretion increased more gradually, and no direct side-chain oxidation of [H-3]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.