Degradation of 24S-hydroxycholesterol in men is not regulated by CYP7A1
C. Knabe, T. Sudhop, K. von Bergmann, D. Lütjohann
Department of Clinical Pharmacology, University of Bonn, Germany
DOI 10.5414/CPP45577
Abstract
Objective: The conversion of cholesterol into bile acids occurs via a long cascade of enzymatically regulated oxidative processes. Our aim was to examine if an upregulation of hepatic cholesterol 7a-hydroxylase (CYP7A1) in humans by cholestyramine, a bile acid-binding resin, has an effect on the degradation of brain-specific 24S-hydroxycholesterol. Patients and methods: Six normocholesterolemic male volunteers received 4 g cholestyramine b.i.d. for 2 weeks in an open, prospective exploratory trial. Serum concentrations of lipoproteins and triglycerides were measured by routine enzymatic assays. Sterols and oxysterols were measured by gas chromatography/mass spectrometry. Results: Total and LDL-cholesterol decreased on the average by 9.3% (p = 0.002) and 19.8% (p = 0.001) after 2 weeks of treatment, respectively. Absolute serum concentrations of 7a-hydroxycholesterol, a marker for bile acid production, increased 4-fold after 2 weeks, while 24S- and 27-hydroxycholesterol remained unchanged. Treatment with cholestyramine elevated serum levels of lathosterol, an indicator for the endogenous synthesis of cholesterol, by 146% (p = 0.009). Conclusion: In addition to lowering serum concentrations of total cholesterol and LDL-cholesterol, cholestyramine at a dose rate of 4 g b.i.d. causes a significant increase in the CYP 7A1 catalyzed 7a-hydroxylation of cholesterol and an up-regulation of endogenous cholesterol synthesis, as proven indirectly by an increase in serum lathosterol levels. Total serum levels of 24S- and 27-hydroxycholesterol remained unchanged indicating that an up-regulation in CYP7A1 activity is not responsible for the subsequent oxidative degradation of these hydroxylated sterols.
Author Details
Authors
Departments
- Department of Clinical Pharmacology, University of Bonn, Germany
Address
D. Lütjohann, PhD, Department of Clinical Pharmacology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
Email:
[email protected]
Citation
C. Knabe, T. Sudhop, K. von Bergmann and D. Lütjohann.Degradation of 24S-hydroxycholesterol in men is not regulated by CYP7A1. 2007; 45: 577-582. doi: 10.5414/CPP45577.
