Serum Concentrations of 7α–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.