Skip to main content
Log in

Expression of an ovine growth hormone transgene in mice increases archidonic acid in cellular membranes

  • Papers
  • Published:
Transgenic Research Aims and scope Submit manuscript

Abstract

The degree of unsaturation of membrane lipids has been implicated in a number of physiological disorders, yet its regulation remains poorly understood, especially the regulation of the synthesis and distribution of arachidonic acid levels, the most abundant long chain polyunsaturated fatty acid in membranes. Transgenic mice expressing the ovine metallothionein 1a — ovine growth hormone (oMt1a-oGH) fusion gene exhibited significantly elevated levels of a number of long chain polyusaturated fatty acids in serum, including arachidonic acid. In oMt1a-oGH transgenic mice the products of all three desaturation pathways are affected by the expression of the ovine growth hormone trangene. The essential precursors of membrane long chain polyunsturated fatty acids, 18:2n-6 and 18:3n-3, were reduced in transgenic relative to controls, and their desaturation and elongation products, arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3), were elevated. As rare intermediate long chain polyunsaturated fatty acids such as eicosatrienoic acid (20:3n-9) were also signficantly elevated, we conclude that these observations reflect increased activity of the Δ-5 and Δ-6 desaturase enzymes. In contranst, the products of the stearoyl CoA or Δ-9 desaturase, were significantly reduced in oMt1a-oGH expressing transgenics relative to their levels in control mice.

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.

Similar content being viewed by others

References

  • Bazzoni, G., Dejana, E. and Del, M.A. (1991) Platelet-neutrophil interactions. Possible relevance in the pathogenesis of thrombosis and inflammation.Haematological 76, 491–99.

    CAS  Google Scholar 

  • Berger, A. and German, J.B. (1990) Phospholipid fatty acid composition of various mouse tissues after feeding alphalinolenate (18:3n-3) or eicosatrienoate (20:3n-3).Lipids 25, 473–80.

    CAS  PubMed  Google Scholar 

  • Bouillon, R. (1991) Growth hormone and bone.Horm. Res. 1, 49–55.

    Google Scholar 

  • Brenner, R.R. (1990) Endocrine control of fatty acid desaturation.Biochem. Soc. Trans. 18, 773–5.

    CAS  PubMed  Google Scholar 

  • Catania, A., Arnold, J., Macaluso, A., Hiltz, M.E. and Lipton, J.M. (1991) Inhibition of acute inflammation in the periphery by central action of salicylates.Proc. Natl Acad. Sci. USA 88, 8544–7.

    CAS  PubMed  Google Scholar 

  • Chen, Y.Q., Liu, B., Tang, D.G. and Honn, K.V. (1992) Fatty acid modulation of tumor cell-platelet-vessel wall interaction.Cancer Metastasis Rev. 11, 389–409.

    Article  CAS  PubMed  Google Scholar 

  • Chow, J.C., Murray, J.D., Pomp, D., Baldwin, R.L., Calvert, C.C. and Oberbauer, A.M. (1994) Regulation of insulin-like grwoth factor-I and binding protein-3 expression in oMt1a-oGH transgenic mice.Transgenic Res. 3, 127–33.

    Article  CAS  PubMed  Google Scholar 

  • Clarke, R.J., Mayo, G., Price, P. and FitzGerald, G.A. (1991) Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin.N. Engl. J. Med. 325, 1137–41.

    CAS  PubMed  Google Scholar 

  • FitzGerald, G.A. (1991) Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists.Am. J. Cardiology 68, 11B-5B.

    CAS  Google Scholar 

  • Garris, R.E. and Kirkwood, C.F. (1989) Misorprostol: a prostaglandin E1 analogue.Clin. Pharm. 8, 627–44.

    CAS  PubMed  Google Scholar 

  • Ho, K.Y. and Kelly, J.J. (1991) Role of growth hormone in fluid homeostasis.Horm. Res. 1, 44–8.

    Google Scholar 

  • Holub, B.J., Philbrick, D.J., Parbtani, A. and Clark, W.F. (1991) Dietary lipid modification of renal disorders and ether phospholipid metabolism.Biochem. Cell Biol. 69, 485–9.

    CAS  PubMed  Google Scholar 

  • Huang, Y.S., Mills, D.E. Ward, R.P., Simmons, V.A. and Horrobin, D.F. (1990) Stress modulates cholesterol-induced changes in plasma and liver fatty acid composition in rats fed n-6 fatty acid-rich oils.Proc. Soc. Exp. Biol. Med. 195, 136–41.

    CAS  PubMed  Google Scholar 

  • Kaiser, E., Chiba, P. and Zaky, K. (1990) Phospholipases in biology and medicine.Clin. Biochem. 23, 349–70.

    CAS  PubMed  Google Scholar 

  • Kawashima, Y., Uy, Y.N. and Kozuka, H. (1989) Sex-related differences in the enhancing effects of perfluoro-octanoic acid on stearoyl-CoA desaturase and its influence on the acyl composition of phospholipid in rat liver. Comparison with clofibric acid and tiadenol.Biochem. J. 263, 897–904.

    CAS  PubMed  Google Scholar 

  • Keller, U. and Miles, J.M. (1991) Growth hormone and lipids.Horm. Res. 1, 36–40.

    Google Scholar 

  • Kinsella, J.E., Lokesh, B. and Stone, R.A. (1990) Dietary n-3 polyusaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms.Am. J. Clinn. Nutr. 52, 1–28.

    CAS  Google Scholar 

  • Lewis, R.A., Austen, K.F. and Soberman, R.J. (1990) Leukotrienes and other products of the 5-lipoxygenase pathway.N. Engl. J. Med. 323, 645–55.

    CAS  PubMed  Google Scholar 

  • Makheja, A.N. (1992) Atherosclerosis: the eicosanoid connection.Mol. Cell. Biochem. 111, 137–42.

    Article  CAS  PubMed  Google Scholar 

  • Meftah, N.M. and Skett, P. (1989) The role of microsomal phospholipids and their fatty acid composition in the control of hepatic metabolism of lignocaine.Br. J. Pharmacol. 98, 1399–405.

    CAS  PubMed  Google Scholar 

  • Mildner, A.M. and Clarke, S.D. (1991) Porcines fatty acid synthase: cloning of a complementary DNA, tissue distribution of its mRNA and suppression of expression by somatotropin and dietary protein.J. Nutr. 121, 900–7.

    CAS  PubMed  Google Scholar 

  • Moller, N., Jorgensen, J.O., Abildgard, N., Orskov, L., Schmitz, O. and Christiansen, J.S. (1991) Effects of grwoth hormone on glucose metabolism.Horm. Res. 1, 32–5.

    Google Scholar 

  • Nakada, T., Kwee, I.L. and Ellis, W.G. (1990) Membrane fatty acid composition shows delta-6-desaturase abnormalities in Alzheimer's disease.Neuroreport 1, 153–5.

    CAS  PubMed  Google Scholar 

  • Navarro, X., Canete, J.D., Prat, J. and Segura, R. (1988) Fatty acids of plasma and red blood cell lipids in a normal population.Rev. Esp. Fisiol. 44, 387–93.

    CAS  PubMed  Google Scholar 

  • Oberbauer, A.M., Currier, T.A., Nancarrow, C.D., Ward, K.A. and Murray, J.D. (1992) Longitudinal bone growth of oMt1a-oGH transgenic male mice.Amer. J. Physiol. 262, E936–42.

    CAS  PubMed  Google Scholar 

  • Oscarsson, J. and Eden, S. (1988) Sex differences in fatty acid composition of rat liver phosphatidylcholine are regulated by the plasma pattern of growth hormone.Biochim. Biophys. Acta 959, 280–7.

    CAS  PubMed  Google Scholar 

  • Oscarsson, J., Jansson, J.O. and Eden, S. (1988) Plasma pattern of growth hormone regulates sexual differentition of phosphatidylcholine in rat plasma.Acta. Physiol. Scand. 133, 257–65.

    CAS  PubMed  Google Scholar 

  • Pace-Asciak, C. (1989) One-step rapid extractive methylation of plasma nonesterified fatty acids for gas chromatographic analysis.J. Lipid Res. 30, 451–4.

    CAS  PubMed  Google Scholar 

  • Pomp, D., Murray, J.D. and Medrano, J.F. (1991) Single day detection of transgenic mice by PCR of toe clips.Mouse Genome 89, 279.

    Google Scholar 

  • Pomp, D., Nancarrow, C.D., Ward, K.A. and Murray, J.D. (1992) Growth, feed efficiency and body composition of transgenic mice expressing a sheep metallothionein 1a-sheep growth hormone fusion gene.Livestock Prod. Sci. 31, 335–50.

    Article  Google Scholar 

  • Roebuck, B.D. (1992) Dietary fat and the development of pancreatic cancer.Lipids 27, 804–6.

    CAS  PubMed  Google Scholar 

  • Searle, T.W., Murray, J.D. and Baker, P.J. (1992) The effect of increased growth hormone production on body composition in mice — transgenic vs control.J. Endo. 132, 285–91.

    CAS  Google Scholar 

  • Shanahan, C.M., Rigby, N.W., Murray, J.D., Marshall, J.T., Townrow, C.A., Nancarrow, C.D. and Ward, K.A. (1989) Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusions gene in transgenic mice.Mol. Cell Biol. 9, 5473–9.

    CAS  PubMed  Google Scholar 

  • Sprecher, H. (1991) Enzyme activities affecting tissue lipid fatty acid composition.World Rev. Nutr. Diet 66, 166–76.

    CAS  PubMed  Google Scholar 

  • Wodtke, E. and Cossins, A.R. (1991) Rapid cold-induced changes of membrane order and delta 9-desaturase activity in endoplasmic reticulum of carp liver: a time-course study of thermal acclimation.Biochim. Biophys. Acta 1064, 343–50.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murray, J.D., Oberbauer, A.M., Sharp, K.R. et al. Expression of an ovine growth hormone transgene in mice increases archidonic acid in cellular membranes. Transgenic Research 3, 241–248 (1994). https://doi.org/10.1007/BF02336777

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02336777

Keywords

Navigation