The enterohepatic physiology of 24,25-dihydroxyvitamin D₃

Products of intravenously administered [³H]24,25-dihydroxyvitamin D₃ are excreted in the bile of normocalcemic, vitamin D-replete rats. Within 3 and 24 hr, 7.3% ± 1.4 and 18.5% ± 1.4 (mean ± S.D.) of the administered dose appears in the bile. Three hours after the instillation of the biliary products of [³H]24,25-dihydroxyvitamin D₃ into the duodena of other rats, 7.6% ± 2.05 of the administered dose appears in newly secreted bile; at 24 hr 21.1% ± 7.8 of the instilled dose is present in newly secreted bile. These data suggest that products of 24,25-dihydroxyvitamin D₃ are excreted in bile and undergo an enterohepatic circulation. The metabolites of 24,25-dihydroxyvitamin D₃ excreted in bile are much more polar than the parent sterol as assessed by silicic acid chromatography and by high-performance liquid chromatographic techniques. The products are retained on DEAE-cellulose in the presence of methanol are eluted upon the addition of acetic acid to the eluting solvent. The data support the existence of a quantitatively important enterohepatic circulation of polar metabolites of [³H]24,25-dihydroxyvitamin D₃; disturbances in this metabolic pathway could help explain the pathogenesis of hepatic and intestinal osteodystrophy.