Chronic Suppression of Cholesterol 7α-Hydroxylase by Dietary Chenodeoxycholic Acid in Neonatal Guinea Pigs: Its Effect on Subsequent Bile Acid Metabolism in the Adult

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.