Relationship between the serum concentration of 7 alpha-hydroxycholesterol and fecal bile acid excretion in humans.
BACKGROUND
Serum levels of 7 alpha-hydroxycholesterol have been shown to reflect the activity of cholesterol 7 alpha-hydroxylase, the key enzyme of bite acid synthesis in the liver, but a comparison with direct measurements of bile acid synthesis rates has never been performed.


METHODS
7 alpha-Hydroxycholesterol was measured by gas-liquid chromatography/mass spectrometry and bile acid synthesis by the fecal balance method in 35 subjects.


RESULTS
A significant correlation was found between 7 alpha-hydroxycholesterol concentration in serum and bile acid synthesis (r = 0.863, p < 0.001). Serum levels of 7 alpha-hydroxycholesterol in 20 patients treated with a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor did not differ from levels obtained in healthy volunteers (78 +/- 7 ng/ml versus 63 +/- 5 ng/ml; NS). Treatment with fenofibrate reduced 7 alpha-hydroxycholesterol concentrations in six patients from 107 +/- 47 ng/ml to 61 +/- 12 ng/ml (p < 0.05).


CONCLUSIONS
We conclude that the concentration of 7 alpha-hydroxycholesterol in serum is an indicator of bile acid synthesis and that serum levels of 7 alpha-hydroxycholesterol are not affected in patients treated with HMG-CoA reductase inhibitors but are affected in those treated with fenofibrate.
Hahn
C
C
Dept. of Clinical Pharmacology, University of Bonn, Germany.
von Bergmann
K
K
D000214:Acyl Coenzyme A / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000032:analysis / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D005243:Feces / Q000737:chemistry*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D006937:Hypercholesterolemia / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D008659:Metabolic Diseases / Q000378:metabolism; D008875:Middle Aged
D000214:Acyl Coenzyme A; D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; D000960:Hypolipidemic Agents; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; C011724:cholest-5-en-3 beta,7 alpha-diol; D011345:Fenofibrate