Hassan A S, Yunker R L, Sprinkle D J, Subbiah M T
J Nutr. 1983 May;113(5):986-95. doi: 10.1093/jn/113.5.986.
Treatment of neonatal guinea pigs with cholestyramine persistently increases the activity of hepatic cholesterol 7 alpha-hydroxylase (CH-7 alpha), the rate-limiting enzyme of bile acid biosynthesis. In this study, we examined whether CH-7 alpha activity could be persistently inhibited by manipulations (chenodeoxycholic acid feeding) during neonatal life. Male Hartley guinea pigs (2-3 days old) were fed 0.25% chenodeoxycholic acid (CDCA)-supplemented diet for 10 days or 6 weeks. Feeding CDCA for 10 days increased plasma cholesterol [controls (C), 25 +/- 3 vs. CDCA, 34 +/- 2 mg/dl]. Bile acid pool in animals fed CDCA for 10 days was nearly fivefold greater than controls (C, 5.8 +/- 0.3 vs. CDCA, 29.1 +/- 0.9 mg/100 g body weight), whereas CH-7 alpha activity was almost completely inhibited [C, 1.83 +/- 0.4 vs. CDCA, 0.02 +/- 0.02 pmol/(mg . minute)]. Four weeks after stopping CDCA feeding, CH-7 alpha was greater in the CDCA-fed animals (C, 0.47 +/- 0.03 vs. CDCA, 0.67 +/- 0.05). This was associated with a greater bile acid pool in these animals (C, 3.0 +/- 0.2 vs. CDCA, 5.8 +/- 0.4). We conclude that CDCA fed to neonatal guinea pigs inhibits CH-7 alpha activity. This inhibition is not permanent, however, since CH-7 alpha activity increases following withdrawal from chronic CDCA feeding.
用消胆胺治疗新生豚鼠会持续增加肝胆固醇7α-羟化酶（CH-7α）的活性，该酶是胆汁酸生物合成的限速酶。在本研究中，我们检测了新生期通过某些操作（喂食鹅去氧胆酸）是否能持续抑制CH-7α的活性。雄性哈特利豚鼠（2 - 3日龄）喂食添加0.25%鹅去氧胆酸（CDCA）的饲料10天或6周。喂食CDCA 10天会使血浆胆固醇升高[对照组（C），25±3 vs. CDCA组，34±2 mg/dl]。喂食CDCA 10天的动物胆汁酸池比对照组大近五倍（C组，5.8±0.3 vs. CDCA组，29.1±0.9 mg/100 g体重），而CH-7α活性几乎完全被抑制[C组，1.83±0.4 vs. CDCA组，0.02±0.02 pmol/（mg·分钟）]。停止喂食CDCA四周后，CDCA喂养组动物的CH-7α活性更高（C组，0.47±0.03 vs. CDCA组，0.67±0.05）。这与这些动物中更大的胆汁酸池相关（C组，3.0±0.2 vs. CDCA组，5.8±0.4）。我们得出结论，喂食新生豚鼠CDCA会抑制CH-7α活性。然而，这种抑制并非永久性的，因为在长期CDCA喂养停止后CH-7α活性会增加。
