1. The biliary excretion of 25-hydroxy-[3H]-vitamin D3 (25-(OH)-[3H]D3)-derived materials after the intravenous administration of 25-(OH)-[3H]D3 (1.25 nmol/100 g body weight) was studied during a period of 3 h in homozygous (icteric) and heterozygous (anicteric) Gunn rats.
2. The heterozygous rats excreted significantly more 25-(OH)-[3H]D3-derived materials than the homozygous Gunn rats (7.2 ± 1.5% vs 3.1 ± 0.5% of the administered dose, P<0.025).
3. The lower biliary excretion of 25-(OH)-[3H]-D3-derived material in homozygous compared with heterozygous Gunn rats was not due to differences in the plasma 25-(OH)-[3H]D3 concentrations nor was it due to differences in the uptake of 25-(OH)-[3H]D3 by the liver since similar liver/plasma concentration ratios were observed in both groups of animals; it seemed, however, to be due to differences in the biliary transfer of 25-(OH)-[3H]-D3, as indicated by a lower bile/liver concentration ratio in homozygous than in heterozygous rats (1.39 ± 0.23 vs 0.49 ± 0.06, P<0.05).
4. Moreover, samples of bile obtained from homozygous rats contained no β-glucuronidase-sensitive 25-(OH)-[3H]D3-derived materials but contained significantly more intact 25-(OH)-[3H]-D3 than samples obtained from heterozygous Gunn rats (P<0.05). After hydrolysis of bile obtained from homozygous and heterozygous Gunn rats with the enzyme β-glucuronidase, the total amount of intact 25-(OH)-[3H]D3 recovered was found to be similar in the two groups of rats.
5. The results of the present experiments indicate that conjugation of 25-(OH)D3 with glucuronic acid is one of the metabolic pathways involved in its biliary transfer; they also illustrate that the homozygous Gunn rats constitute a good model to study the importance and biological significance of the glucuronidation pathway in the biliary excretion of vitamin D sterols.