Skip to main content
Log in

Human sterol 12α-hydroxylase (CYP8B1) is mainly expressed in hepatocytes in a homogenous pattern

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

The liver is the only organ where the complete synthesis of bile acids takes place. The present study was undertaken to investigate whether regional differences exist within the individual human hepatic lobuli regarding the pattern of expression of sterol 12α-hydroxylase (CYP8B1), a key enzyme in bile acid synthesis. A specific anti-human CYP8B1 peptide antiserum was developed and used for Western blotting and hepatic immunostaining of livers from various patients. CYP8B1 in human liver was expressed in the cytoplasm of hepatocytes with an even nonzonal distribution within the liver lobulus. Pericentral expression was confirmed for CYP2E1. A weak staining was noted in cholangiocytes and Kupffer cells. Previous studies on hepatic CYP27A1 and CYP7A1 in rats have shown a zonal expression, primarily in the pericentral region. Our studies indicate a different pattern for CYP8B1 expression in human liver, which was even rather than zonal.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Andersson U, Eggertsen G, Björkhem I (1998) Rabbit liver contains one major sterol 12alpha-hydroxylase with broad substrate specificity. Biochim Biophys Acta 1389(2):150–154

    CAS  PubMed  Google Scholar 

  • Andersson U, Yang YZ, Björkhem I, Einarsson C, Eggertsen G, Gåfvels M (1999) Thyroid hormone suppresses hepatic sterol 12alpha-hydroxylase (CYP8B1) activity and messenger ribonucleic acid in rat liver: failure to define known thyroid hormone response elements in the gene. Biochim Biophys Acta 1438(2):167–174

    CAS  PubMed  Google Scholar 

  • Björkhem I, Eggertsen G (2001) Genes involved in initial steps of bile acid synthesis. Curr Opin Lipidol 12(2):97–103

    Article  PubMed  Google Scholar 

  • Chiang JY (1998) Regulation of bile acid synthesis. Front Biosci 3:d176–d193

    CAS  PubMed  Google Scholar 

  • Eggertsen G, Olin M, Andersson U, Ishida H, Kubota S, Hellman U, Okuda KI, Björkhem I (1996) Molecular cloning and expression of rabbit sterol 12alpha-hydroxylase. J Biol Chem 271(50):32269–32275

    Article  CAS  PubMed  Google Scholar 

  • Einarsson K, Akerlund JE, Reihner E, Björkhem I (1992) 12 alpha-hydroxylase activity in human liver and its relation to cholesterol 7 alpha-hydroxylase activity. J Lipid Res 33(11): 1591–1595

    CAS  PubMed  Google Scholar 

  • Erickson SK, Lear SL, Tyler D, Maher J (2000) Liver cell distribution of expression of enzymes and nuclear transcription factors involved in regulation of bile acid synthesis. In: XIVth international bile acid meeting: biology of bile acids in health and disease. p 14

  • Gåfvels M, Olin M, Chowdhary BP, Raudsepp T, Andersson U, Persson B, Jansson M, Björkhem I, Eggertsen G (1999) Structure and chromosomal assignment of the sterol 12alpha-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns. Genomics 56(2):184–196

    Article  PubMed  Google Scholar 

  • Groothuis GM, Hardonk MJ, Renston RH, Wong KY, Karlaganis G, Paumgartner G (1982) Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport. Am J Physiol 243(6):G455–G462

    CAS  PubMed  Google Scholar 

  • Ingelman-Sundberg M, Johansson I, Penttilä KE, Glaumann H, Lindros KO (1988) Centrilobular expression of ethanol-inducible cytochrome P-450 (IIE1) in rat liver. Biochem Biophys Res Commun 157(1):55–60

    CAS  PubMed  Google Scholar 

  • Ishida H, Noshiro M, Okuda K, Coon MJ (1992) Purification and characterization of 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase. J Biol Chem 267(30):21319–21323

    CAS  PubMed  Google Scholar 

  • Johansson I, Ekström G, Scholte B, Puzycki D, Jörnvall H, Ingelman-Sundberg M (1988) Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies. Biochemistry 27(6):1925–1934

    Article  CAS  PubMed  Google Scholar 

  • Jones AL, Hradek GT, Renston RH, Wong KY, Karlaganis G, Paumgartner G (1980) Autoradiographic evidence for hepatic lobular concentration gradient of bile acid derivative. Am J Physiol 238(3):G233–G237

    CAS  PubMed  Google Scholar 

  • Li-Hawkins J, Gåfvels M, Olin M, Lund EG, Andersson U, Schuster G, Björkhem I, Russell DW, Eggertsen G (2002) Cholic acid mediates negative feedback regulation of bile acid synthesis in mice. J Clin Invest 110(8):1191–1200

    Article  CAS  PubMed  Google Scholar 

  • Massimi M, Lear SR, Huling SL, Jones AL, Erickson SK (1998) Cholesterol 7alpha-hydroxylase (CYP7A): patterns of messenger RNA expression during rat liver development. Hepatology 28(4):1064–1072

    Article  CAS  PubMed  Google Scholar 

  • Twisk J, Hoekman MF, Mager WH, Moorman AF, de Boer PA, Scheja L, Princen HM, Gebhardt R (1995) Heterogeneous expression of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase genes in the rat liver lobulus. J Clin Invest 95(3):1235–1243

    CAS  PubMed  Google Scholar 

  • Vlahcevic ZR, Eggertsen G, Björkhem I, Hylemon PB, Redford K, Pandak WM (2000) Regulation of sterol 12alpha-hydroxylase and cholic acid biosynthesis in the rat. Gastroenterology 118(3):599–607

    CAS  PubMed  Google Scholar 

  • van Waarde WM, Verkade HJ, Wolters H, Havinga R, Baller J, Bloks V, Muller M, Sauer PJ, Kuipers F (2002) Differential effects of streptozotocin-induced diabetes on expression of hepatic ABC-transporters in rats. Gastroenterology 122(7):1842–1852

    PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from The Swedish Research Council, The Swedish Heart and Lung Foundation, The Swedish Society for Medicine, Wallenberg Consortium North, and the Julin Foundation. We are thankful to Dr. Magnus Ingelman-Sundberg, Karolinska Institutet, for providing us with antibodies against the rat CYP2E1.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mats Gåfvels.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J., Greene, S., Eriksson, L.C. et al. Human sterol 12α-hydroxylase (CYP8B1) is mainly expressed in hepatocytes in a homogenous pattern. Histochem Cell Biol 123, 441–446 (2005). https://doi.org/10.1007/s00418-005-0779-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-005-0779-0

Keywords

Navigation