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Oxidative stress in hypopituitary dwarf mice and in transgenic mice overexpressing human and bovine GH

AGE volume 22, pages 181–186 (1999)Cite this article

Abstract

Growth hormone (GH) stimulates metabolic activity. The purpose of this study was to examine whether it is involved in the aging process by increasing oxidative stress. Inorganic peroxides and lipid peroxides were measured in kidney and liver samples in dwarf mice that are deficient in GH, prolactin and thyrotropin and in transgenic mice that produce high levels of GH. In normal male mice, there was an increase in inorganic peroxides in the kidney with age. Levels were lower in old male dwarfs when compared with normal male mice of similar age. Unexpectedly, concentrations of inorganic peroxides were frequently lower in transgenic male and female mice expressing extra copies of GH than in normal controls. Lipid peroxide concentrations were more variable. Transgenic animals expressing bovine GH had the highest levels of lipid peroxides. In dwarfs, kidney levels were similar to those of normal mice but concentrations in the liver were more variable. This study does not indicate that the decrease in life span in transgenic mice producing high levels of GH is due to an increase of oxidative stress. Rather, it suggests that expression of extra copies of the GH gene may lead to a compensatory increase in antioxidant protection.

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References

  • Bartke, A, Brown-Borg, H.M., Bode, A.M., Carlson, J.C., Hunter, W.S. and Bronson, R.T. (1998) Does growth hormone prevent or accelerate aging? Exp. Gerontol. 33, 675–687.

    PubMed  CAS  Article  Google Scholar 

  • Bartke, A. (1979) Genetic models in the study of anterior pituitary hormones. In, Genetic Variation in Hormone Systems, (ed. Shire, J.G.M.). CRC Press, Boca Raton, pp113–126.

    Google Scholar 

  • Bell, R., Carlson, J.C., Storr, K.C., Herbert, K. and Sivak, J. (1999) High fructose feeding of streptozotocin (STZ)-diabetic rats is associated with increased cataract formation and increased oxidative stress in the kidney. Br. J.Nutr. in press.

  • Beyer-Mears, A., Ku, L. and Cohen, M.P. (1984) Glomerular polyol accumulation in diabetes and its prevention by oral sorbinil. Diabetes, 33, 604–607.

    PubMed  CAS  Google Scholar 

  • Bradford, M.M. (1976) a rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254.

    PubMed  CAS  Article  Google Scholar 

  • Brown-Borg, H. M., Borg, K. E., Meliska, C. J. and Bartke, A, (1996) Dwarf mice and the aging process. Nature, 384, 33.

    PubMed  CAS  Article  Google Scholar 

  • Carlson, J.C. and Forbes, W.F. (1992) The free radical theory of aging: A critique and unresolved questions. Can. J. Aging, 11, 262–268.

    Google Scholar 

  • Cecim, M., Bartke, A., Yun, J.S. and Wagner, T.E. (1994) Expression of human, but not bovine, growth hormone genes promotes development of mammary tumors in transgenic mice. Transgenics, 1, 431–437.

    CAS  Google Scholar 

  • Chandrashekar, V. and Bartke, A. (1993) Induction of endogenous insulin-like growth factor-1 secretion alters the hypothalamic-pituitary-testicular function in growth hormone-deficient adult dwarf mice. Biol. Reprod. 48: 544–551.

    PubMed  CAS  Article  Google Scholar 

  • Halliwell, B. and Gutteridge, J.M.C. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219,1–14.

    PubMed  CAS  Google Scholar 

  • Harman, D. (1981) The aging process. Proc. Natl. Acad. Sci. 78, 7124–7128.

    PubMed  CAS  Google Scholar 

  • Hauck, S.J. and Bartke, A. (1999) Effects of growth hormone (GH) status on hypothalamic antioxidant enzymes (AOEs). Free Rad. Biol. Med. in press.

  • Hunter, W.S. Croson, W.B., Bartke, A., Gentry, M.V. and Meliska, C.J. (1999) Low body temperature on long-lived Ames dwarf mice at rest and during stress. Physiol. Behav. 67, 433–437.

    PubMed  CAS  Article  Google Scholar 

  • Hunt, J.V., Dean, R.T. and Wolff S.P. (1988) Hydroxyl radical production and autoxidative glycosylation. Biochem. J. 256, 205–212.

    PubMed  CAS  Google Scholar 

  • Kajiura, L.J. and Rollo, C.D. (1994) A mass budget for transgenic “supermice” engineered with extra growth hormone genes: evidence for energetic limitation. Can. J. Zool. 72, 1010–1017.

    Article  Google Scholar 

  • McGrane, M.M., deVente, J., Yun, J., Bloom, J., Park, E., Wynshaw-Boris, A., Wagner, T., Rottman, F.M. and Hanson, RW. (1988) Tissue-specific expression and dietary regulation of a chimeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic mice. J. Biol. Chem. 263, 11443–11451.

    Google Scholar 

  • Meiattini, F. (1985) Inorganic peroxides. In, Methods of enzymatic analysis, 2nd ed., (eds. Bernt, E, Bergmeyer, H.). Academic Press, New York, pp 566–571.

    Google Scholar 

  • Orr, W.C. and Sohal, R.S. (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263, 1128–1130.

    PubMed  CAS  Google Scholar 

  • Palmiter, R.D., Brinster, R.L., Hammer, R.E., Trumbauer, M.E., Rosenfeld, MG., Birnberg, N.C. and Evans, R.M. (1982) Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature, 300, 611–615.

    PubMed  CAS  Article  Google Scholar 

  • Pryor, W.A. (1987) The free-radical theory of aging revisited: A critique and a suggested disease-specific theory. In, Modern Biological Theories of Aging, (eds. Warner, H.R., Butler, R.N., Spott, R.L. and Schneider, E.L.). Raven Press, New York, pp 89–112.

    Google Scholar 

  • Rollo, C.D., Carlson, J.C. and Sawada, M. (1996) Giant transgenic “supermice” exhibit accelerated aging consistent with the free radical theory. Can. J. Zool. 74, 606–620.

    CAS  Google Scholar 

  • Sawada, M and Carlson, J.C. (1985) Association of lipid peroxidation during luteal regression in the rat and natural aging in the rotifer. Exp. Gerontol. 20, 179–186.

    PubMed  CAS  Article  Google Scholar 

  • Sawada, M., Sester, U. and Carlson, J.C. (1992) Superoxide radical formation and associated biochemical alterations in the plasma membrane of brain, heart, and liver during the lifetime of the rat. J. Cell. Biochem 48, 296–304.

    PubMed  CAS  Article  Google Scholar 

  • Sawada, M. and Carlson, J.C. (1996) Intracellular regulation of progesterone secretion by the superoxide radical in the rat corpus luteum. Endocrinology, 137, 1580–1584.

    PubMed  CAS  Article  Google Scholar 

  • Scanes, C.G. (1995) Growth hormone action: protein metabolism. In Growth Hormone, (eds. Harvey, S. Scanes, C.G., Daughaday, W.H.). CRC Press, Boca Raton, pp 389–391.

    Google Scholar 

  • Scanes, C.G. (1995) Growth hormone action: carbohydrate metabolism. In Growth Hormone, (eds Harvey, S., Scanes, C.G., Daughaday, W.H.). CRC Press, Boca Raton, pp 371–377.

    Google Scholar 

  • Shi, L., Sawada, M., Sester, U. and Carlson, J.C. (1994) Alterations in free radical activity in aging Drosophila. Exp. Gerontol. 29, 575–584.

    PubMed  CAS  Article  Google Scholar 

  • Sornson, M.W., Wu, W., Dasen, J.S., Flynn, S.E., Norman, D.J., O’Connell, S.M., Gukovsky, I., Carriere, C. Ryan, A.K., Miller, A.P., Zuo, L., Gleiberman, A.S., Anderson, B., Beamer, W.G. and Rosenfeld, M.G. (1996) Pituitary lineage determination by the prophet of pit-1 homeodomain factor defective in Ames dwarfism. Nature 384: 327–333.

    PubMed  CAS  Article  Google Scholar 

  • Steger, R.W., Bartke, A. and Cecim, M. (1993) Premature aging in transgenic mice expressing different growth hormone genes. J Reprod Fert Suppl 46, 61–75.

    CAS  Google Scholar 

  • Steger, R.W., Bartke, A., Parkening, T.A., Collins, T., Cerven, R., Yun, J.S. and Wagner, T.E. (1994) Effects of chronic exposure to bovine growth hormone (bGH) on the hypothalamic-pituitary axis in transgenic mice: relationship to the degree of expression of the PEPCK-bGH hybrid gene. Transgenics, 1, 245–253.

    CAS  Google Scholar 

  • Sugino, N. Takamori, M.H., Zhong, L., Telleria, C.M. Shiota, K. and Gibori, G. (1998) Hormone regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase messenger ribonucleic acid in the rat corpus luteum. Biol. Reprod. 59, 599–605.

    PubMed  CAS  Article  Google Scholar 

  • Tsushima, T. and Friesen, H.G. (1973) Radioreceptor assay for growth hormone. J. Clin. Endocrinol. Metab. 37, 334–337.

    PubMed  CAS  Article  Google Scholar 

  • Uchiyama, M. and Mihara, M. (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal. Biochem. 86, 271–278.

    PubMed  CAS  Article  Google Scholar 

  • Williamson, J.R., Chang, K., Frangos, M., Hasan, K.S., Ido, Y., Kawamura, T., Nyengaard, J.R., Van Den Eden, M., Kilo, C. and Tilton, R.G. (1993) Hyperglycemic Pseudohypoxia and diabetic complications. Diabetes, 42, 801–811.

    PubMed  CAS  Google Scholar 

  • Wolff, S.W.P. and Dean R.T. (1987) Glucose autoxidation and protein modification. Biochem. J. 245, 243–250.

    PubMed  CAS  Google Scholar 

  • Yu, B.P. (1994) Cellular defenses against damage from reactive oxygen species. Physiol. Rev. 74,139–162.

    PubMed  CAS  Google Scholar 

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Affiliations

  1. Biology Department, University of Waterloo, Waterloo, Ontario, Canada, N2L 3G1

    J. C. Carlson & R. Bharadwaj

  2. Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, 62901-6512

    A. Bartke

Authors
  1. J. C. Carlson
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  2. R. Bharadwaj
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  3. A. Bartke
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Carlson, J.C., Bharadwaj, R. & Bartke, A. Oxidative stress in hypopituitary dwarf mice and in transgenic mice overexpressing human and bovine GH. AGE 22, 181–186 (1999). https://doi.org/10.1007/s11357-999-0021-4

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  • DOI: https://doi.org/10.1007/s11357-999-0021-4

Keywords

  • Oxidative Stress
  • Growth Hormone
  • Lipid Peroxide
  • Transgenic Mouse
  • Prolactin