Kuroki S, Muramoto S, Kuramoto T, Hoshita T
J Pharmacobiodyn. 1983 Aug;6(8):551-7. doi: 10.1248/bpb1978.6.551.
The effects of dietary cholesterol and sitosterol on the activity of the hepatic steroid 12 alpha-hydroxylase, gallbladder bile acid composition, and serum and liver cholesterol concentrations were studied in female hamsters. The 12 alpha-hydroxylase activity was inhibited by 63% in cholesterol-fed animals and by 30% in sitosterol-fed animals. Cholesterol feeding increased percentages of chenodeoxycholic and lithocholic acids in gallbladder bile with reciprocal decrease of cholic acid, while sitosterol feeding had no significant effect on bile acid composition. Cholesterol feeding increased levels of serum and liver cholesterol, on the contrary, sitosterol decreased both concentrations. A positive correlation between the 12 alpha-hydroxylase activity and the ratio of cholic acid plus its metabolites to chenodeoxycholic acid plus its metabolite was also observed. These results support the proposal that steroid 12 alpha-hydroxylase is a major factor in determining the relative proportion of cholic acid and chenodeoxycholic acid synthesized in the liver and indicate that cholesterol feeding increased percentage of chenodeoxycholic acid by inhibiting the activity of steroid 12 alpha-hydroxylase.
在雌性仓鼠中研究了膳食胆固醇和谷甾醇对肝脏类固醇12α-羟化酶活性、胆囊胆汁酸组成以及血清和肝脏胆固醇浓度的影响。在喂食胆固醇的动物中，12α-羟化酶活性受到63%的抑制，在喂食谷甾醇的动物中受到30%的抑制。喂食胆固醇会增加胆囊胆汁中鹅去氧胆酸和石胆酸的百分比，同时胆酸相应减少，而喂食谷甾醇对胆汁酸组成没有显著影响。喂食胆固醇会增加血清和肝脏胆固醇水平，相反，谷甾醇会降低这两种浓度。还观察到12α-羟化酶活性与胆酸及其代谢产物与鹅去氧胆酸及其代谢产物的比例之间存在正相关。这些结果支持了类固醇12α-羟化酶是决定肝脏中合成的胆酸和鹅去氧胆酸相对比例的主要因素这一观点，并表明喂食胆固醇通过抑制类固醇12α-羟化酶的活性增加了鹅去氧胆酸的百分比。
