Skip to main content

In situ localization of transthyretin-mRNA in the adult human liver, choroid plexus and pancreatic islets and in endocrine tumours of the pancreas and gut

Summary

In situ hybridization with 35S-labeled single stranded RNA probes was used on sections from formaldehyde-fixed and paraffin-embedded tissue specimens to provide semiquantitative data on the occurrence of transthyretin(TTR)-mRNA in human liver, choroid plexus and pancreatic islets as well as in 15 endocrine tumours of the pancreas and gut. A monoclonal antibody to TTR was used for immunocytochemical identification of the protein in consecutive sections.

The amount of TTR-mRNA in hepatocytes was found to be much less than that in epithelial cells of the choroid plexus. Glucagon cells of the pancreatic islets were also specifically labeled and the level of TTR-mRNA in these cells was intermediate between that of hepatocytes and choroid plexus epithelial cells. Four glucagonomas, one malignant insulinoma and two midgut carcinoids were shown to contain TTR-mRNA. The ‘in situ’ labeled cells were also found to be TTR immunoreactive. These findings present the first conclusive evidence for TTR synthesis in pancreatic islets and in endocrine tumours. They also establish that the high serum concentration of TTR found in some patients with endocrine tumours (notably glucagonomas) is most likely due to tumour production of TTR.

This is a preview of subscription content, access via your institution.

References

  • Aleshire SL, Bradley CA, Richardson LD, Parl FF (1983) Localization of human prealbumin in choroid plexus epithelium. J Histochem Cytochem 31:608–612

    Google Scholar 

  • Burton PM, Horner BL, Jones GH, Lin T, Nestor JJ Jr, Newman SR, Parks TL, Smith AJ, White A (1987) Immuno-enhancing activity of the amino-terminal domain of human prealbumin: isolation, characterization and synthesis. Int J Immunopharmacol 9:297–305

    Google Scholar 

  • Bussolati G, Papotti M, Sapino A (1984) Binding of antibodies against human prealbumin to intestinal and bronchial carcinoids and to pancreatic endocrine tumours. Virchows Arch (Cell Pathol) 45:15–22

    Google Scholar 

  • Collins VP, Jacobsson B, Pettersson T, Carlström A (1986) Monoclonal antibodies to transthyretin. Scand J Clin Lab Invest 46:761–769

    Google Scholar 

  • Cox NH, DeLeon DV, Angerer LM, Angerer RC (1984) Detection of mRNAs in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol 101:485–502

    Google Scholar 

  • Dickson PW, Howlett GJ, Schreiber G (1985) Rat transthyretin (prealbumin): Molecular cloning, nucleotide sequence and gene expression in liver and brain. J Biol Chem 260:8214–8219

    Google Scholar 

  • Dickson PW, Aldred AR, Marley PD, Bannister D, Schreiber G (1986) Rat choroid plexus specializes in the synthesis and the secretion of transthyretin (prealbumin). J Biol Chem 261:3475–3478

    Google Scholar 

  • Eiden LE (1987) Is chromogranin a prohormone? Nature 325:301

    Google Scholar 

  • Felding P, Fex G (1982) Cellular origin of prealbumin in the rat. Biochim Biophys Acta 716:446–449

    Google Scholar 

  • Goodman DS (1976) Retinol-binding protein, prealbumin and vitamin A transport. In: Jamieson GA, Grenwalt TJ (eds) Trace components of plasma: isolation and clinical significance. Alan R Liss, New York, pp 313–330

    Google Scholar 

  • Grimelius L, Wilander E (1980) Silver stains in the study of endocrine cells of the gut and pancreas. Invest Cell Pathol 3:3–12

    Google Scholar 

  • Harper ME, Marselle LM, Gallo RC, Wong-Staal F (1986) Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci USA 83:772–776

    Google Scholar 

  • Hayashi S, Gillam IC, Delaney AD, Tener GM (1978) Acetylation of chromosome squashes of Drosophila melanogaster decreases the background in autoradiographs from hybridization with 125I-labeled RNA. J Histochem Cytochem 26:677–679

    Google Scholar 

  • Herbert J, Wilcox JN, Pham KTC, Fremeau RT, Zeviani M, Dwork A, Soprano DR, Makover A, Goodman DS, Zimmerman EA, Roberts JL, Schon EA (1986) Transthyretin: A choroid plexus-specific transport protein in human brain. Neurology 36:900–911

    Google Scholar 

  • Jacobsson B, Pettersson T, Sandstedt B, Carlström A (1979) Prealbumin in the islets of Langerhans. IRCS Med Sci 7:590

    Google Scholar 

  • Jacobsson B, Collins VP, Grimelius L, Pettersson T, Sandstedt B, Carlström A (1988a) Transthyretin immunoreactivity in human and porcine liver, choroid plexus and pancreatic islets. J Histochem Cytochem (in press)

  • Jacobsson B, Carlström A, Collins VP, Grimelius L (1988b) Transthyretin in endocrine pancreatic tumours. Am J Pathol (in press)

  • Jörnvall H, Carlström A, Pettersson T, Jacobsson B, Persson M, Mutt V (1981) Structural homologies between prealbumin, gastrointestinal prohormones and other proteins. Nature 291:261–263

    Google Scholar 

  • Kato M, Kato K, Blaner WS, Chertow BS, Goodman DS (1985) Plasma and cellular retinoid-binding proteins and transthyretin (prealbumin) are all localized in the islets of Langerhans in the rat. Proc Natl Acad Sci USA 82:2488–2492

    Google Scholar 

  • Liddle CN, Reid WA, Kennedy JS, Miller ID, Horne CHW (1985) Immunolocalization of prealbumin: Distribution in normal human tissue. J Pathol 146:107–113

    Google Scholar 

  • Miller ID, Reid WA, Liddle CN, Horne CHW (1984) Immunologicalization of prealbumin as a marker for carcinoid tumours. J Pathol 143:199–204

    Google Scholar 

  • Rajatanavin R, Liberman C, Lawrence GD, D'arcangues CM, Young RA, Emerson CH (1985) Euthyroid hyperthyroxinemia and thyroxine-binding prealbumin excess in islet cell carcinoma. J Clin Endocrinol Metab 61:17–21

    Google Scholar 

  • Rask L, Valtersson C, Anundi H, Kvist S, Eriksson U, Dallner G, Peterson PA (1983) Subcellular localization in normal and vitamin A-deficient rat liver of vitamin A serum transport proteins, albumin ceruloplasmin and class I major histocompatibility antigens. Exp Cell Res 143:91–102

    Google Scholar 

  • Robbins J, Bartalena L (1986) Plasma transport of thyroid hormones. In: Hennemann G (ed) Thyroid hormone metabolism. Marcel Dekker, New York, pp 3–38

    Google Scholar 

  • Rondana M, Milani L, Merkel C, Caregaro L, Gatta A (1987) Value of prealbumin plasma levels as liver test. Digestion 37:72–78

    Google Scholar 

  • Schreiber G, Aldred AR, Thomas T, Birch HE, Dickson PW, Guo-Fen T, Heinrich PC, Northemann W, Howlett GJ, DeJong FA, Mitchell A (1986) Levels of messenger ribonucleic acids for plasma proteins in rat liver during acute experimental inflammation. Inflammation 10:59–66

    Google Scholar 

  • Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS (1985) Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat. J Biol Chem 260:11793–11798

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jacobsson, B. In situ localization of transthyretin-mRNA in the adult human liver, choroid plexus and pancreatic islets and in endocrine tumours of the pancreas and gut. Histochemistry 91, 299–304 (1989). https://doi.org/10.1007/BF00493004

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00493004

Keywords

  • Glucagon
  • Human Liver
  • Pancreatic Islet
  • Insulinoma
  • Endocrine Tumour