Serum Concentrations of 7α–Hydroxy–4–Cholesten–3–One Reflect Bile Acid Synthesis in Humans

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Abstract
Serum concentrations of 7α–hydroxy–4–cholesten–3–one (α–HC) have recently been shown to reflect the activity of cholesterol 7α–hydroxylase in humans. To evaluate the relationship between α–HC in serum and bile acid synthesis, serum concentrations of α–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 α–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). α–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 α–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 α–hydroxylase activity and that α–HC in serum may serve as a convenient marker for the semiquantitative assessment of bile acid synthesis in humans.

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