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We compared the intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with Crohn's disease and resections of the small bowel. Patients were subgrouped into those with small (less than 100 cm), intermediate (100-300 cm), and large (greater than 300 cm) resections. [3H]cholecalciferol or [3H]25-hydroxycholecalciferol were given orally and serial blood samples were taken for measurement of plasma radiolabeled vitamin. Absorption of both forms of the vitamin decreased with extent of resection but 25-hydroxycholecalciferol absorption was always greater than that of cholecalciferol. When compared with normal control subjects, 25-hydroxycholecalciferol absorption in these patients was better maintained than that of cholecalciferol. These data indicate that vitamin D malabsorption reflects the extent of distal small-bowel resection in Crohn's disease. Treatment with oral cholecalciferol is sufficient in those with small or moderate resections but oral 25-hydroxycholecalciferol supplementation may be preferred in those with a severe short-bowel syndrome.

A pathway has been described in the skin for the synthesis of 24-dehydrovitamin D3 (delta 24D3) from 24-dehydroprovitamin D3. The physiologic function of delta 24D3 is unknown, but has been proposed as a potential inhibitor of hepatic vitamin D-25-hydroxylase. We validated an assay for vitamin D-25-hydroxylase in rat hepatic microsomes, using nanomolar amounts of [3H]D3 as substrate, and found that delta 24D3 competitively inhibits vitamin D-25-hydroxylase activity. The apparent Ki was approximately 17 nM, indistinguishable from the Km of approximately 15 nM, suggesting that both delta 24D3 and cholecalciferol have similar affinity for the enzyme. We found no [3H]delta 24D3 in serum or liver extracts after repletion of vitamin D-depleted rats with [3H]vitamin D3 for 4 h or 6 days. A dose of 1 microgram delta 24D3 to vitamin D- and calcium-depleted rats was unable to promote any elevation in the 45Ca transport by everted duodenal sacs or to increase levels of plasma calcium: thus no evidence for biological conversion of delta 24D3 to vitamin D3 was observed. Further studies are needed to determine whether delta 24D3 is released from the skin to the circulation and is taken up by the liver, before physiological relevance can be attributed to this inhibitor.

Hepatic vitamin D-25-hydroxylase activity is greater in vitamin D-depleted than replete animals. We investigated whether vitamin D itself or a metabolite of vitamin D was responsible for modulating the activity of vitamin D-25-hydroxylase. Accordingly, we repleted vitamin D-depleted rats with subcutaneous injections of 2600, 520, and 130 pmoles of cholecalciferol (D3), 25-hydroxycholecalciferol (25(OH)D3), and 1,25-dihydroxycholecalciferol (1,25(OH)2D3), respectively, for up to 3 weeks. Repletion resulted in accelerated weight gain and in increased activity of gut mucosal alkaline phosphatase. Using an improved assay to measure vitamin D-25-hydroxylase activity in liver homogenates, we found 78% reduction (P less than 0.001) in the D3-repleted group, maximal by 1 week, in contrast to no change in those groups treated with D3 metabolites. D3, 25(OH)D3, and D3-esters remaining in livers at the time of assay were estimated in a parallel experiment using [3H]D3-repleted rats. Residual D3 accounted for only a 9% dilution of substrate in the assay. 25(OH)D3 was present in the liver at concentrations two orders of magnitude lower than the amount required to inhibit vitamin D-25-hydroxylase activity in vitro. D3 esters had no inhibitory effect in vitro at 250-fold excess of that found in the repleted rat liver. Vitamin D appears to modulate its D-25-hydroxylase activity in biological systems by a mechanism other than feedback inhibition by 25(OH)D3, 1,25(OH)2D3, or D3-esters.