Journal of Hepatology
Volume 52, Issue 5 , Pages 705-711 , May 2010

Bile acids modulate glucocorticoid metabolism and the hypothalamic–pituitary–adrenal axis in obstructive jaundice

  • Alison D. McNeilly

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44 1382 496589; fax: +44 1382 633923.
    • ,
  • David P. Macfarlane

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • ,
  • Emmett O’Flaherty

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • ,
  • Dawn E. Livingstone

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • ,
  • Tijana Mitić

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • ,
  • Kirsty M. McConnell

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • ,
  • Scott M. McKenzie

      Affiliations

    • MRC Blood Pressure Group, Glasgow Cardiovascular Research Centre, University of Glasgow,126 University Place, Glasgow G12 8TA, UK
    • ,
  • Eleanor Davies

      Affiliations

    • MRC Blood Pressure Group, Glasgow Cardiovascular Research Centre, University of Glasgow,126 University Place, Glasgow G12 8TA, UK
    • ,
  • Rebecca M. Reynolds

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • ,
  • Helle C. Thiesson

      Affiliations

    • Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense C, Denmark
    • ,
  • Ole Skøtt

      Affiliations

    • Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense C, Denmark
    • ,
  • Brian R. Walker

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    • ,
  • Ruth Andrew

      Affiliations

    • Endocrinology Unit, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

Received 2 August 2009 ,Revised 30 September 2009 ,Accepted 15 October 2009.

References 

  1. Harry R, Auzinger G, Wendon J. The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology. 2002;36:395–402
  2. Tsai MH, Peng YS, Chen YC, Liu NJ, Ho YP, Fang JT, et al. Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. Hepatology. 2006;43:673–681
  3. Fernandez J, Escorsell A, Zabalza M, Felipe V, Navasa M, Mas A, et al. Adrenal insufficiency in patients with cirrhosis and septic shock. Hepatology. 2006;44:1288–1295
  4. Swain MG, Patchev V, Vergalla J, Chrousos G, Jones EA. Suppression of hypothalamic–pituitary–adrenal axis responsiveness to stress in a rat model of acute cholestasis. J Clin Invest. 1993;91:1903–1908
  5. Demelia L, Solinas A, Poma R, Vallebona E, Pitzus F. Hypothalamo–pituitary–adrenal function in liver cirrhosis of viral etiology. Ann Ital Med Int. 1991;6:203–209
  6. Stewart PM, Burra P, Shackleton CH, Sheppard MC, Elias E. 11beta-Hydroxysteroid dehydrogenase deficiency and glucocorticoid status in patients with alcoholic and non-alcoholic chronic liver disease. J Clin Endocrinol Metab. 1993;76:748–751
  7. Stimson RH, Andersson J, Andrew R, Redhead DN, Karpe F, Hayes PC, et al. Cortisol release from adipose tissue by 11βHSD1 in humans. Diabetes. 2009;58:46–53
  8. Ackermann D, Vogt B, Escher G, Dick B, Reichen J, Frey BM, et al. Inhibition of 11βHSD by bile acids in rats with cirrhosis. Hepatology. 1999;30:623–629
  9. Danielsson H, Sjovall J. Bile acid metabolism. Annu Rev Biochem. 1975;44:233–253
  10. Edwards CR, Stewart PM, Burt D, Brett L, McIntyre MA, Sutanto WS, et al. Localisation of 11βHSD – tissue specific protector of the mineralocorticoid receptor. Lancet. 1988;2:986–989
  11. Frey FJ. Impaired 11βHSD contributes to renal sodium avidity in cirrhosis: hypothesis or fact?. Hepatology. 2006;44:795–801
  12. Quattropani C, Vogt B, Odermatt A, Dick B, Frey BM, Frey FJ. Reduced activity of 11βHSD in patients with cholestasis. J Clin Invest. 2001;108:1299–1305
  13. Thiesson HC, Jensen BL, Bistrup C, Ottosen PD, McNeilly AD, Andrew R, et al. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11βHSD2 activity. Am J Physiol Regul Integr Comp Physiol. 2007;292:R625–R636
  14. Escher G, Nawrocki A, Staub T, Vishwanath BS, Frey BM, Reichen J, et al. Down-regulation of hepatic and renal 11βHSD in rats with liver cirrhosis. Gastroenterology. 1998;114:175–184
  15. Diederich S, Grossmann C, Hanke B, Quinkler M, Herrmann M, Bahr V, et al. In the search for specific inhibitors of human 11beta-HSDs: chenodeoxycholic acid selectively inhibits 11beta-HSD-I. Eur J Endocrinol. 2000;142:200–207
  16. Morris DJ, Souness GW, Latif SA, Hardy MP, Brem AS. Effect of chenodeoxycholic acid on 11βHSD in various target tissues. Metabolism. 2004;53:811–816
  17. Latif SA, Hartman LR, Souness GW, Morris DJ. Possible endogenous regulators of steroid inactivating enzymes and glucocorticoid-induced Na+ retention. Steroids. 1994;59:352–356
  18. Bertolotti M, Spady DK, Dietschy JM. Regulation of hepatic cholesterol metabolism in the rat in vivo: effect of a synthetic fat-free diet on sterol synthesis and low-density lipoprotein transport. Biochim Biophys Acta. 1995;1255:293–300
  19. Barat P, Livingstone DE, Elferink CM, McDonnell CR, Walker BR, Andrew R. Effects of gonadectomy on glucocorticoid metabolism in obese Zucker rats. Endocrinology. 2007;148:4836–4843
  20. Livingstone DE, Jones GC, Smith K, Jamieson PM, Andrew R, Kenyon CJ, et al. Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology. 2000;141:560–563
  21. Charbonneau A, The VL. Genomic organization of a human 5beta-reductase and its pseudogene and substrate selectivity of the expressed enzyme. Biochim Biophys Acta. 2001;1517:228–235
  22. Wigler M, Silverstein S, Lee LS, Pellicer A, Cheng Y, Axel R. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell. 1977;11:223–232
  23. Voice MW, Seckl JR, Chapman KE. The sequence of 5′ flanking DNA from the mouse 11βHSD1 gene and analysis of putative transcription factor binding sites. Gene. 1996;181:233–235
  24. Paterson JM, Morton NM, Fievet C, Kenyon CJ, Holmes MC, Staels B, et al. Metabolic syndrome without obesity: hepatic overexpression of 11βHSD1 in transgenic mice. Proc Natl Acad Sci USA. 2004;101:7088–7093
  25. Lo S, Russell JC, Taylor AW. Determination of glycogen in small tissue samples. J Appl Physiol. 1970;28:234–236
  26. Schwarz M, Russell DW, Dietschy JM, Turley SD. Marked reduction in bile acid synthesis in cholesterol 7alpha-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia. J Lipid Res. 1998;39:1833–1843
  27. Ye P, Kenyon CJ, MacKenzie SM, Seckl JR, Fraser R, Connell JM, et al. Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II. Endocrinology. 2003;144:3321–3328
  28. Best R, Walker BR. Additional value of measurement of urinary cortisone and unconjugated cortisol metabolites in assessing the activity of 11βHSD in vivo. Clin Endocrinol. 1997;47:231–236
  29. Jin Y, Stayrook SE, Albert RH, Palackal NT, Penning TM, Lewis M. Crystal structure of human type III 3αHSD/bile acid binding protein complexed with NADP(+) and ursodeoxycholate. Biochemistry. 2001;40:10161–10168
  30. Naito T, Kuroki S, Chijiiwa K, Tanaka M. Bile acid synthesis and biliary hydrophobicity during obstructive jaundice in rats. J Surg Res. 1996;65:70–76
  31. Fukuhara Y, Hirasawa A, Li X-K, Kawasaki M, Fujino M, Funeshima N, et al. Gene expression profile in the regenerating rat liver after partial hepatectomy. J Hepatol. 2003;38:784–792
  32. Festi D, Morselli-Labate AM, Roda A, Bazzoli F, Frabboni R, Rucci P, et al. Diagnostic effectiveness of serum bile acids in liver diseases as evaluated by multivariate statistical methods. Hepatology. 1983;3:707–713
  33. Westerbacka J, Yki-Jarvinen H, Vehkavaara S, Hakkinen AM, Andrew R, Wake DJ, et al. Body fat distribution and cortisol metabolism in healthy men: enhanced 5beta-reductase and lower cortisol/cortisone metabolite ratios in men with fatty liver. J Clin Endocrinol Metab. 2003;88:4924–4931
  34. Dallman MF, Akana SF, Laugero KD, Gomez F, Manalo S, Bell ME, et al. A spoonful of sugar: feedback signals of energy stores and corticosterone regulate responses to chronic stress. Physiol Behav. 2003;79:3–12
  35. Jamieson A, Wallace AM, Andrew R, Nunez BS, Walker BR, Fraser R, et al. Apparent cortisone reductase deficiency: a functional defect in 11βHSD1. J Clin Endocrinol Metab. 1999;84:3570–3574
  36. Gustafsson JA, Stenberg A. Neonatal programming of androgen responsiveness of liver of adult rats. J Biol Chem. 1974;249:719–723
  37. Hohenester S, Oude-Elferink RP, Beuers U. Primary biliary cirrhosis. Semin Immunopathol. 2009;31:283–307

☆ Funding: This work was supported by grants from the Wellcome Trust, British Heart Foundation, Society for Endocrinology, Medical Research Council, Danish Heart Foundation, and Danish Society of Hypertension.

PII: S0168-8278(10)00094-2

doi: 10.1016/j.jhep.2009.10.037

Journal of Hepatology
Volume 52, Issue 5 , Pages 705-711 , May 2010

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