Skip to main content
NCBI home page
Gut logoLink to Gut
. 1993 Nov;34(11):1601–1606. doi: 10.1136/gut.34.11.1601

Down regulation of epidermal growth factor receptors in liver proliferation induced by a mixture of triiodothyronine, amino acids, glucagon, and heparin (TAGH).

D A Vesey 1, A C Selden 1, H J Hodgson 1
PMCID: PMC1374430  PMID: 8244150

Abstract

This study investigated the mechanisms by which TAGH solution (a mixture of triiodothyronine, amino acids, glucagon, and heparin) induces DNA synthesis in hepatocytes in the liver of intact rats, with particular reference to events at the epidermal growth factor (EGF) receptor. Both partial hepatectomy and infusion of TAGH stimulated DNA synthesis at 24 hours and both procedures resulted in a reduction of EGF receptors assessed in plasma membranes isolated from rat liver at this time. In cell cultures, while EGF strongly stimulated DNA synthesis and started EGF receptor down regulation, TAGH had only a minor effect (1.5 x basal) on DNA synthesis and did not interact with or down regulate the EGF receptor. Membrane phosphorylation studies, however, showed that TAGH induced phosphorylation of tyrosine residues in the EGF receptor. The in vivo action of TAGH seems to entail recruitment of similar changes in the EGF receptor to those that occur after partial hepatectomy.

Full text

PDF
1601

Images in this article

1603Figure 3
on p.1603
1604Figure 4
on p.1604
1604Figure 5
on p.1604

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson N. N., Jr, Touster O. Isolation of rat liver plasma membrane fragments in isotonic sucrose. Methods Enzymol. 1974;31:90–102. doi: 10.1016/0076-6879(74)31009-9. [DOI] [PubMed] [Google Scholar]
  2. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner D. A., Koch K. S., Leffert H. L. Transforming growth factor-alpha stimulates proto-oncogene c-jun expression and a mitogenic program in primary cultures of adult rat hepatocytes. DNA. 1989 May;8(4):279–285. doi: 10.1089/dna.1.1989.8.279. [DOI] [PubMed] [Google Scholar]
  4. Bucher N. L., Patel U., Cohen S. Hormonal factors and liver growth. Adv Enzyme Regul. 1977 Oct 3;16:205–213. doi: 10.1016/0065-2571(78)90074-2. [DOI] [PubMed] [Google Scholar]
  5. Earp H. S., O'Keefe E. J. Epidermal growth factor receptor number decreases during rat liver regeneration. J Clin Invest. 1981 May;67(5):1580–1583. doi: 10.1172/JCI110190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gladhaug I. P., Christoffersen T. Rapid constitutive internalization and externalization of epidermal growth factor receptors in isolated rat hepatocytes. Monensin inhibits receptor externalization and reduces the capacity for continued endocytosis of epidermal growth factor. J Biol Chem. 1988 Sep 5;263(25):12199–12203. [PubMed] [Google Scholar]
  7. Marti U., Burwen S. J., Jones A. L. Biological effects of epidermal growth factor, with emphasis on the gastrointestinal tract and liver: an update. Hepatology. 1989 Jan;9(1):126–138. doi: 10.1002/hep.1840090122. [DOI] [PubMed] [Google Scholar]
  8. Massagué J. Transforming growth factor-alpha. A model for membrane-anchored growth factors. J Biol Chem. 1990 Dec 15;265(35):21393–21396. [PubMed] [Google Scholar]
  9. McGowan J. A., Strain A. J., Bucher N. L. DNA synthesis in primary cultures of adult rat hepatocytes in a defined medium: effects of epidermal growth factor, insulin, glucagon, and cyclic-AMP. J Cell Physiol. 1981 Sep;108(3):353–363. doi: 10.1002/jcp.1041080309. [DOI] [PubMed] [Google Scholar]
  10. Mead J. E., Fausto N. Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1558–1562. doi: 10.1073/pnas.86.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Michalopoulos G. K. Liver regeneration: molecular mechanisms of growth control. FASEB J. 1990 Feb 1;4(2):176–187. [PubMed] [Google Scholar]
  12. Munro H. N. The determination of nucleic acids. Methods Biochem Anal. 1966;14:113–176. doi: 10.1002/9780470110324.ch5. [DOI] [PubMed] [Google Scholar]
  13. Okamoto M., Karasik A., White M. F., Kahn C. R. Epidermal growth factor stimulated phosphorylation of a 120-kilodalton endogenous substrate protein in rat hepatocytes. Biochemistry. 1990 Oct 9;29(40):9489–9494. doi: 10.1021/bi00492a023. [DOI] [PubMed] [Google Scholar]
  14. Rubin R. A., O'Keefe E. J., Earp H. S. Alteration of epidermal growth factor-dependent phosphorylation during rat liver regeneration. Proc Natl Acad Sci U S A. 1982 Feb;79(3):776–780. doi: 10.1073/pnas.79.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schacterle G. R., Pollack R. L. A simplified method for the quantitative assay of small amounts of protein in biologic material. Anal Biochem. 1973 Feb;51(2):654–655. doi: 10.1016/0003-2697(73)90523-x. [DOI] [PubMed] [Google Scholar]
  16. Selden C., Hodgson H. J. Further characterisation of 'hepatotropin', a high molecular weight hepatotrophic factor in rat serum. J Hepatol. 1989 Sep;9(2):167–176. doi: 10.1016/0168-8278(89)90047-0. [DOI] [PubMed] [Google Scholar]
  17. Short J., Brown R. F., Husakova A., Gilbertson J. R., Zemel R., Lieberman I. Induction of deoxyribonucleic acid synthesis in the liver of the intact animal. J Biol Chem. 1972 Mar 25;247(6):1757–1766. [PubMed] [Google Scholar]
  18. Vesey D. A., Cunningham J. M., Selden A. C., Woodman A. C., Hodgson H. J. Dimethyl sulphoxide induces a reduced growth rate, altered cell morphology and increased epidermal-growth-factor binding in Hep G2 cells. Biochem J. 1991 Aug 1;277(Pt 3):773–777. doi: 10.1042/bj2770773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vesey D. A., Woodman A. C., Hodgson H. J. Galactosamine induced hepatitis induces a reduction in hepatocyte epidermal growth factor receptors. Gut. 1992 Jul;33(7):954–958. doi: 10.1136/gut.33.7.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wollenberg G. K., Harris L., Farber E., Hayes M. A. Inverse relationship between epidermal growth factor induced proliferation and expression of high affinity surface epidermal growth factor receptors in rat hepatocytes. Lab Invest. 1989 Feb;60(2):254–259. [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES