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Accumulation of 7α-hydroxycholesterol in liver tissue of patients with cholesterol gallstones

  • Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Patients with cholesterol gallstones have a reduced pool of bile acids. This study was undertaken to clarify the mechanism by which bile acid biosynthesis does not increase to supranormal levels to cause a reexpansion of the pool. We investigated the first two steps of the bile acid biosynthesis pathway by assaying the activities of cholesterol 7α-hydroxylase, the rate-limiting enzyme in this pathway, and 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase, and by measuring the concentrations of 7α-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one in liver specimens from ten patients with cholesterol gallstones and ten gallstone-free controls. In the patients with gallstones, cholesterol 7α-hydroxylase activity, 3β-hydroxy-Δ5-C27 dehydrogenase/isomerase activity, and hepatic 7α-hydroxy-4-cholesten-3-one concentration did not significantly different from levels in controls, but hepatic 7α-hydroxycholesterol concentration was more than twofold that of controls (12.9 ± 2.6 vs 5.3 ±1.2 nmol/g liver,P<0.01). The concentration of 7α-hydroxycholesterol positively correlated with the ratio of cholesterol 7α-hydroxylase activity to 3β-hydroxy-Δ5-C27 dehydrogenase/isomerase activity (r=0.93;P<0.005) in the gallstone-free controls. In contrast, this correlation disappeared in the patients with gallstones. These results suggest a derangement of the normal 7α-hydroxycholesterol metabolism in the patients with gallstones. The reason for the accumulation of 7α-hydroxycholesterol remains unclear; however, it is possible that, in patients with cholesterol gallstones, the accumulated 7α-hydroxycholesterol causes inappropriate suppression of cholesterol 7α-hydroxylase activity by product inhibition.

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Authors and Affiliations

  1. Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, 305, Tsukuba, Japan

    Akira Honda, Tadashi Yoshida, Naomi Tanaka, Yasushi Matsuzaki, Bingfang He, Junichi Shoda & Toshiaki Osuga

Authors
  1. Akira Honda
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  2. Tadashi Yoshida
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  3. Naomi Tanaka
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  4. Yasushi Matsuzaki
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  5. Bingfang He
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  6. Junichi Shoda
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  7. Toshiaki Osuga
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Honda, A., Yoshida, T., Tanaka, N. et al. Accumulation of 7α-hydroxycholesterol in liver tissue of patients with cholesterol gallstones. J Gastroenterol 30, 651–656 (1995). https://doi.org/10.1007/BF02367793

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  • DOI: https://doi.org/10.1007/BF02367793

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