Species difference in cholesterol 7alpha-hydroxylase expression of rabbit and rat liver microsomes after bile duct ligation.

BACKGROUND: Bile duct ligation (BDL) produces a good animal model for investigation of the metabolic changes in obstructive jaundice. The aim of this study was to investigate the species difference in expression of cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) in rabbits and rats after BDL. MATERIALS AND METHODS: Ten male New Zealand white rabbits weighing 2.5-3 kg and 12 male Wistar strain rats weighing 250-300 g were used. Half the animals underwent BDL, and half were sham operated (Sham). The animals were sacrificed on day 5 after operation. The livers were harvested, and levels of mRNA and 7alpha-hydroxylase activity were determined. Concentrations of serum bilirubin and bile acids were also measured. RESULTS: In BDL rats, the levels of mRNA were increased 30%, and 7alpha-hydroxylase activity was three times that of the Sham group. In BDL rabbits, however, these values were approximately 60 and 50% lower than the Sham group, respectively. Serum bile acid concentrations increased up to 13 times in BDL rabbits and 70 times in BDL rats over that of the Sham groups. Serum cholesterol and serum total bilirubin concentration also increased after BDL in both animals. CONCLUSION: These results suggest that there is a species difference in the expression of 7alpha-hydroxylase after BDL in rabbits and rats and the reason for this difference is most likely pretranslational regulation.

A comparative study of the conversion of 7-hydroxycholesterol in rabbit, guinea pig, rat, hamster, and chicken.

The metabolism of epimeric 7-hydroxycholesterol was studied in vitro. 7Alpha-hydroxycholesterol or 7beta-hydroxycholesterol were incubated with rabbit, guinea pig, rat, hamster, and chicken microsomal suspensions and then extracted and analyzed using high-performance liquid chromatography (HPLC). 7Alpha-hydroxy-4-cholesten-3-one was the main product from 7alpha-hydroxycholesterol in the rabbit, guinea pig, and rat. A considerable amount of 7-ketocholesterol was also produced in the hamster and chicken. In all vertebrates, 7beta-hydroxycholesterol was converted only to 7-ketocholesterol in all vertebrates. 7Beta-hydroxy-4-cholesten-3-one was not detected. Reduction of 7-ketocholesterol was also studied in the rat and hamster. Whereas 7-ketocholesterol was converted to 7beta-hydroxycholesterol in the rat, it was converted to both 7alpha- and 7beta-hydroxycholesterol in the hamster. These results suggest that 7alpha-hydroxycholesterol is converted not only to 7alpha-hydroxy-4-cholesten-3-one but also to 7-ketocholesterol in the hamster and chicken. 7Beta-hydroxycholesterol was converted to 7-ketocholesterol in all vertebrates tested. The interconversion between 7alpha- and 7beta-hydroxycholesterol via 7-ketocholesterol was observed in the hamster in this in vitro study.