Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one reflect bile acid synthesis in humans.
Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (alpha-HC) have recently been shown to reflect the activity of cholesterol 7 alpha-hydroxylase in humans. To evaluate the relationship between alpha-HC in serum and bile acid synthesis, serum concentrations of alpha-HC, and rates of bile acid synthesis, as measured by the isotope dilution technique using gas chromatography-mass spectrometry, were determined simultaneously. Regression analysis revealed a positive linear correlation of serum alpha-Hc with synthesis of cholic acid (CA) (r = .59, P = .02), chenodeoxycholic acid (CDCA) (r = .75, P = .001), and total synthesis of both primary bile acids (r = .83, P < .001) in patients with gallstones and normal liver function (n = 15). alpha-HC was also correlated to input rates of deoxycholic acid (DCA) (r = .53, P <.05). Addition of patients with chronic cholestatic liver disease (n = 5) improved the correlation between serum alpha-HC and synthesis of CA (r = .75, P < .001), CDCA (r = .77, P < .001), and both primary bile acid combined (r = .87), P < .001). Our data are in agreement with the concept that synthesis of bile acids is regulated by cholesterol 7 alpha-hydroxylase activity and that alpha-HC in serum may serve as a convenient marker for the semiquantitative assessment of bile acid synthesis in humans.
Sauter
G
G
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
Berr
F
F
Beuers
U
U
Fischer
S
S
Paumgartner
G
G
D000328:Adult; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001835:Body Weight; D002247:Carbon Isotopes; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002769:Cholelithiasis / Q000097:blood / Q000378:metabolism*; D002779:Cholestasis / Q000097:blood / Q000378:metabolism*; D002783:Cholestenones / Q000097:blood*; D003903:Deuterium; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011865:Radioisotope Dilution Technique
D001647:Bile Acids and Salts; D015415:Biomarkers; D002247:Carbon Isotopes; D002783:Cholestenones; C002656:7 alpha-hydroxy-4-cholesten-3-one; D003903:Deuterium; D001663:Bilirubin