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Expression patterns of mRNAs for ammoniametabolizing enzymes in the developing rat: the ontogenesis of hepatocyte heterogeneity

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Summary

The expression patterns of the mRNAs for the ammonia-metabolizing enzymes carbamoylphosphate synthetase (CPS), glutamine synthetase (GS) and glutamate dehydrogenase (GDH) were studied in developing pre- and neonatal rat liver byin situ hybridization.

In the period of 11 to 14 embryonic days (ED) the concentrations of GS and GDH mRNA increases rapidly in the liver, whereas a substantial rise of CPS mRNA in the liver does not occur until ED 18. Hepatocyte heterogeneity related to the vascular architecture can first be observed at ED 18 for GS mRNA, at ED 20 for GDH mRNA and three days after birth for CPS mRNA. The adult phenotype is gradually established during the second neonatal week, i.e. GS mRNA becomes confined to a pericentral compartment of one to two hepatocytes thickness, CPS mRNA to a large periportal compartment being no longer expressed in the pericentral compartment and GDH mRNA is expressed over the entire porto-central distance, decreasing in concentration going from central to portal. Comparison of the observed mRNA distribution patterns in the perinatal liver, with published data on the distribution of the respective proteins, points to the occurrence of posttranslational, in addition to pretranslational control mechanisms in the period of ontogenesis of hepatocyte heterogeneity.

Interestingly, during development all three mRNAS are expressed outside the liver to a considerable extent and in a highly specific way, indicating that several organs are involved in the developmentally regulated expression of the mRNAs for the ammonia-metabolizing enzymes, that were hitherto not recognized as such.

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References

  • Assitis, G. M., Tzimagiorgis, G., Mitsialis, A., Zannis, V., Plaitakis, A., Papamatheakis, J. &Moschonas, N. (1988) Isolation and characterization of cDNA clones encoding human liver glutamate dehydrogenase: evidence for a small gene family.Proc. Natl. Acad. Sci. 85, 3494–8.

    Google Scholar 

  • Banner, C., Silverman, S., Thomas, J. W. Lampel, K. A., Vitkovic, L., Huie, D. &Wenthold, R. J. (1987) Isolation of a human brain cDNA for glutamate dehydrogenase.J. Neurochem. 49, 246–52.

    Google Scholar 

  • Bennett, A. L., Paulson, K. E., Miller, R. E. &Darnell Jr, J. E. (1987) Acquisition of antigens characteristics of adult pericentral hepatocytes by differentiating fetal hepatoblastsin vitro.J. Cell Biol. 105, 1073–85.

    Google Scholar 

  • Charles, R., De Graaf, A., Lamers, W. H. &Moorman, A. F. M. (1983) Control of the changes in rat liver carbamoylphosphate synthetase (ammonia) protein levels during ontogenesis. Evidence for changes in immunoreactivity of the protein.Mech. Aging Dev. 22, 193–203.

    Google Scholar 

  • Das, A. T., Moerer, P., Charles, R., Moorman, A. F. M. &Lamers, W. H. (1989) Nucleotide sequence of rat liver glutamatedehydrogenase cDNA.Nucl. Acids Res. 17, 2355.

    Google Scholar 

  • De Groot, C. J,, Van Zonneveld A. J., Mooren, P. G., Zonneveld D., Van Den Dool, A., Van Den Bogaert, A. J. W., Lamers, W. H., Moorman A. F. M. &Charles, R. (1984) Regulation of mRNA levels of rat liver carbamoylphosphate synthetase by glucocorticosteroids and cyclic AMP as estimated with a specific cDNA.Biochem. Biophys. Res. Comm. 124, 882–8.

    Google Scholar 

  • De Groot, C. J., Zonneveld, D., De Laaf, R. T. M., Dingemanse, M. A., Mooren, P. G., Moorman, A. F. M., Lamers, W. H. &Charles, R. (1986) Developmental and hormanal regulation of carbamoylphosphate synthetase gene expression in rat liver: evidence for control mechanisms at diferent levels in the perinatal period.Biochem. Biophys. Acta 866, 61–7.

    Google Scholar 

  • De Groot, C. J., Ten Voorde, C. H. J., Van Andel, R. B., Te Kortschot, A., Gaasbeek Janzen, J. W., Wilson, R. H., Moorman, A. F. M., Charles, R. &Lamers, W. H. (1987) Reciprocal regulation of glutamine synthetase and carbamoylphosphate synthetase levels in rat liver.Biochem. Biophys. Acta 908, 231–40.

    Google Scholar 

  • Feinberg, A. P. &Vogelstein, B. (1984) A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity.Anal. Biochem. 137, 266–7.

    Google Scholar 

  • Gaasbeek Janzen, J. W., Lamers, W. H., Moorman, A. F. M., De Graaf, A., Los, J. A. &Charles, R. (1984) Immunohistochemical localization of carbamoylphosphate synthetase (ammonia) in adult rat liver.J. Histochem. Cytochem. 32, 557–64.

    Google Scholar 

  • Gaasbeek Janzen, J. W., Moorman, A. F. M. Lamers, W. H. &Charles, R. (1985) Development of the heterogeneous distribution of carbamoylphosphate synthetase (ammonia) in rat liver parenchyma during postnatal development.J. Histochem. Cytochem. 339, 1205–11.

    Google Scholar 

  • Gaasbeek Janzen, J. W., Gebhardt, R., Ten Voorde, C. H. J., Lamers, W. H., Charles, R. &Moorman, A. F. M. (1987) Heterogeneous distribution of glutamine synthetase during rat liver development.J. Histochem. Cytochem. 35, 49–54.

    Google Scholar 

  • Gaasbeek Janzen, J. W., Westenend, P. J., Charles, R., Lamers, W. H. &Moorman, A. F. M. (1988) Gene expression in derivatives of the embryonic foregut during prenatal development of the rat.J. Histochem. Cytochem. 36, 1223–30.

    Google Scholar 

  • Gebhardt, R. &Mecke, D. (1983) Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cellsin situ and in primary cultures.Embo. J. 2 567–70.

    Google Scholar 

  • Gumucio, J. J. &Chianale, J. (1988) Liver cell heterogeneity and liver function. In:The Liver Biology and Pathobiology, (edited byArias, I. M., Popper, H., Jakoby, W. B. &Schachter, D.) pp. 931–47. New York: Raven Press.

    Google Scholar 

  • Herzfeld, A. (1972) The distribution of glutamine dehydrogenase in rat tissuesEnzyme 13, 246–51.

    Google Scholar 

  • Holland, P. (1986) In:Manipulating the mouse embryo. A laboratory manual (edited byHogan, B., Constantini, P. &Lacy, E.) pp. 228–42. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.

    Google Scholar 

  • Jungermann, K. (1986) Dynamics of zonal hepatocyte heterogeneity. Perinatal development and adaptive alterations during regeneration after partial hepatectomy, starvation and diabetes.Acta Histochemica 32, 89–98.

    Google Scholar 

  • Knox, W. E. (1979) Enzyme patterns in fetal adult and neoplastic rat tissues. In:Enzymes (edited byDixon, M. &Webb, E. C.) pp. 508–16. London: Longman.

    Google Scholar 

  • Krebs, H. A., &Veech, R. L. (1969) Pyridine nucleotide interrelations. In:The energy level and metabolic control in mitochondria (edited byPapa, S., Tager, J. M., Quagliariello, E., &Slater, E. C.) pp. 329–84. Bari: Adratica Editrice.

    Google Scholar 

  • Krebs, H. A., Hems, R. &Lund, P. (1973) Some regulatory mechanisms in the synthesis of urea in the mammalian liver.Adv. Em. Reg. 11, 361–77.

    Google Scholar 

  • Kuo, F. C., Paulson, K. E. &Darnell, Jr, J. E. (1988) Positional and developmental regulation of glutamine synthetase expression in mouse liver.Mol. Cell Biol. 8, 11, 4966–71.

    Google Scholar 

  • Lamers, W. H. &Mooren, P. G. (1980) Role of glucocorticosteroid hormones on the levels of rat liver carbamoylphosphate synthetase (ammonia) and arginase activity during ontogenesis.Biol. Neonate 37, 113–37.

    Google Scholar 

  • Lamers, W. H. &Mooren, P. G. (1981a) Multihormonal control of enzyme clusters in rat liver ontogenesis. II. Role of glucocorticosteroid and thyroid hormone and of glucagon and insulin.Mech. Aging. Dev. 15, 93–118.

    Google Scholar 

  • Lamers, W. H. &Mooren, P. G. (1981b) Multihormonal control of enzyme clusters in rat liver ontogenesis. I. Effects of adrenalectomy and gonadectomy.Mech. Aging Dev. 15, 77–92.

    Google Scholar 

  • Lamers, W. H., Gaasbeek Janzen, J. W., Te Kortschot, A., Charles, R. &Moorman, A. F. M. (1987) The development of enzymic zonation in liver parenchyma is related to the development of the acinar architecture.Differentiation 35, 228–35.

    Google Scholar 

  • Lamers, W. H., Gaasbeek Janzen, J. W., Moorman, A. F. M., Charles, R., Knecht, E., Martinez-Ramon, A., Hernandez-Yago, J. &Grisolia, S. (1988) Immunohistochemical localization of glutamine dehydrogenase in rat liver; plasticity of the distribution during development and upon hormone treatment.J. Histochem. Cytochem. 36, 41–7.

    Google Scholar 

  • Meister, A. (1984) Enzymology of glutamine. In:Glutamine metabolism in mammalian tissues (edited byHaüssinger, D. &Sies, H.) pp. 3–15. Berlin/Heidelberg. Springer-Verlag.

    Google Scholar 

  • Moorman, A. F. M., De Boer, P. A. J., Geerts, W. J. C., Van de Zande, L. P. G. W., Charles, R. &Lamers W. H. (1988) Complementary distribution of CPS (ammonia) and GS mRNA in adult rat liver detected byin situ hybridization.J. Histochem. Cytochem. 36, 751–5

    Google Scholar 

  • Moorman, A. F. M. Charles, R. & Lamers, W. H. (1989) Development of hepatocyte heterogeneity. In:RBC Cell Biology Reviews: Intercellular hepatocyte heterogeneity (edited byGumucio, J. J.) pp. 27–41. Springer International.

  • Nicoletti, M., Gueri, C. &Grisolia, S. (1977) Turnover of carbamoylphosphate synthetase, of other mitochondrial enzymes and of rat tissues.Eur. J. Biochem. 785, 583–92.

    Google Scholar 

  • Nyunoya, H., Broglie, K. E., Widgren, E. E. &Lusty, C. J. (1985) Characterization and derivation of the gene coding for mitochondrial carbamoyl phosphate syntheetase I of rat.J. Biol. Chem. 260 16, 9346–56.

    Google Scholar 

  • Poliard, A. M., Feldmann, G. &Bernuau, D. (1988) Alpha-fetoprotein and albumin gene transcript are detected in distinct cell populations of the brain and kidney of the developing rat.Differentiation 39, 59–65.

    Google Scholar 

  • Smith, E. L., Austen, B. M., Blumenthal, K. M. andNyc, J. F. (1975) Glutamine dehydrogenases. In:The enzymes (edited byBoyer, P. D.). p. 3 New York: Academic Press.

    Google Scholar 

  • Van de Zande, L. P. G. W., Labruyère, W. I., Smaling, M. M., Moorman, A. F. M., Wilson, R. H., Charles, R. &Lamers, W. H. (1988) Nucleotide sequence of rat GS mRNA.Nucl. Acids. Res. 16, 7726.

    Google Scholar 

  • Van De Zande, L. P. G. W., Labruyère, W. T. Arnberg, A. C., Wilson, R. H., Van Den Bogaert, A. J. W., Das, A. T., Frijters, C., Charles, R. Moorman, A. F. M. & Lamers, W. H. (1989) Isolation and characterization of the rat glutamine synthetase gene.Gene (In press).

  • Van Roon, M. A., Zonneveld, D., Charles, R. &Lamers, W. H. (1988) Accumulation of CPS and PEPCK mRNA in cultures of embryonic rat hepatocytes.Eur. J. Biochem. 178, 191–6.

    Google Scholar 

  • Van Roon, M. A., Aten, J. A., Charles, R. &Lamers, W. H. (1989) The initiations of hepatocyte-specific gene expression within embryonic hepatocytes is a stochastic event.Dev. Biol. 136, 508–16.

    Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy and Embryology, Academic Medical Centre, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    A. F. M. Moorman, P. A. J. De Boer, A. T. Das, W. T. Labruyère, R. Charles & W. H. Lamers

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  1. A. F. M. Moorman
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  2. P. A. J. De Boer
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  3. A. T. Das
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  4. W. T. Labruyère
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  5. R. Charles
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  6. W. H. Lamers
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Moorman, A.F.M., De Boer, P.A.J., Das, A.T. et al. Expression patterns of mRNAs for ammoniametabolizing enzymes in the developing rat: the ontogenesis of hepatocyte heterogeneity. Histochem J 22, 457–468 (1990). https://doi.org/10.1007/BF01007229

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  • DOI: https://doi.org/10.1007/BF01007229

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