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Role of insulin-like growth factor-1 and growth hormone in growth inhibition induced by magnesium and zinc deficiencies

Published online by Cambridge University Press:  09 March 2007

Inge Dørup
Affiliation:
Institute of Physiology, University of Aarhus and Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark
Allan Flyvbjerg
Affiliation:
Institute of Physiology, University of Aarhus and Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark
Maria E. Everts
Affiliation:
Institute of Physiology, University of Aarhus and Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark
Torben Clausen
Affiliation:
Institute of Physiology, University of Aarhus and Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark
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Abstract

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Nutritional deficiencies of magnesium or zinc lead to a progressive and often marked growth retardation. We have evaluated the effect of Mg and Zn deficiency on growth, serum insulin-like growth factor-1 (s-IGF-1), growth hormone (s-GH) and insulin (s-insulin) in young rats. In 3-week-old rats maintained on Mg-deficient fodder for 12 d the weight gain was reduced by about 34%, compared with pair-fed controls. This was accompanied by a 44% reduction in s-IGF-1, while s-insulin showed no decrease. After 3 weeks on Mg-deficient fodder, growth had ceased while serum Mg (s-Mg) and s-IGF-1 were reduced by 76 and 60% respectively. Following repletion with Mg, s-Mg was completely normalized in 1 week, and s-IGF-1 reached control level after 2 weeks. Growth rate increased, but the rats had failed to catch up fully in weight after 3.5 weeks. Absolute and relative pair-feeding were compared during a Mg repletion experiment. Absolute pair-fed animals were given the same absolute amount of fodder as the Mg-deficient rats had consumed the day before. Relative pair-fed animals were given the same amount of fodder, on a body-weight basis, consumed in the Mg-deficient group the day before. In a repletion experiment the two methods did not differ significantly from each other with respect to body-weight, muscle weight, tibia length and s-IGF-1, although there was a tendency towards higher levels in the relative pair-fed group. The peak in s-GH after growth hormone-releasing factor 40 (GRF 40) was 336 (se 63) μg/l in 5-week-old rats that had been Mg depleted for 14 d, whereas age-matched control animals showed a peak of 363 (se 54) μg/l (not significant).

In 3-week-old rats maintained on Zn-deficient fodder for 14 d weight gain was reduced by 83% compared with pair-fed controls. Serum Zn (s-Zn) and s-IGF-1 were reduced by 80 and 69% respectively, while s-insulin was reduced by 66%. The Zn-deficient animals showed a more pronounced growth inhibition than that seen during Mg deficiency and after 17 d on Zn-deficient fodder s-IGF-1 was reduced by 83%. Following repletion with Zn, s-Zn was normalized and s-IGF-1 had increased by 194% (P <0.05) after 3 d. s-IGF-1, however, was not normalized until after 2.5 weeks of repletion. Growth rate increased but the catch-up in weight was not complete during 6 weeks. The maximum increase in s-GH after GRF 40 was 774 (se 61) μg/l in control animals ν. 657 (se 90) μg/l in 6-week-old rats that had been Zn-depleted for 12 d (not significant). In conclusion, both Mg and Zn deficiency lead to growth inhibition that is accompanied by reduced circulating s-IGF-1, but unchanged s-GH response. Zn deficiency, but not Mg deficiency, caused a reduction in s-insulin. The reduction in s-IGF-1 could not be attributed to reduced energy intake, but seems to be a specific effect of nutritional deficiency of Mg or Zn. It is suggested that the growth retardation seen during these deficiency states may be mediated through reduced s-IGF-1 production.

Type
Interaction involving Inorganic Nutrients
Copyright
Copyright © The Nutrition Society 1991

References

REFERENCES

Alleyne, G. A. O. (1970). Studies on total body potassium in malnourished infants. Factors affecting potassium repletion. British Journal of Nutrition 24, 205212.CrossRefGoogle ScholarPubMed
Binz, K., Zapf, J. & Froesch, E. R. (1989). The role of insulin-like growth factor I in growth of diabetic rats. Acta Endocrinologica 121, 628632.Google ScholarPubMed
Bolze, M. S., Reeves, R. D., Lindbeck, F. E. & Elders, M. J. (1987). Influence of zinc on growth, somatomedin, and glycosaminoglycan metabolism in rats. American Journal of Physiology 252, E21E26.Google ScholarPubMed
Caddell, J. L. & Goddard, D. R. (1967). Studies in protein-calorie malnutrition. I. Chemical evidence for magnesium deficiency. New England Journal of Medicine 276, 533535.CrossRefGoogle ScholarPubMed
Cossack, Z. T. (1984). Somatomedin-C in zinc deficiency. Experientia 40, 498500.CrossRefGoogle ScholarPubMed
Dørup, I. & Clausen, T. (1989). Effects of potassium deficiency on growth and protein synthesis in skeletal muscle and the heart of rats. British Journal of Nutrition 62, 269284.CrossRefGoogle ScholarPubMed
Dorup, I. & Clausen, T. (1991). Effects of magnesium and zinc deficiencies on growth and protein synthesis in skeletal muscle and the heart. British Journal of Nutrition 66, 493504.CrossRefGoogle ScholarPubMed
Fliesen, T., Maiter, D., Gerard, G., Underwood, L. E., Maes, M. & Ketelslegers, J.-M. (1989). Reduction of serum insulin-like growth factor I by dietary protein restriction is age dependent. Pediatric Research 26, 415419.CrossRefGoogle ScholarPubMed
Flyvbjerg, A., Dørup, I., Everts, M. E. & Ørskov, H. (1991). Evidence that potassium deficiency induces growth retardation through reduced circulating levels of growth hormone and insulin-like growth factor I. Metabolism 40, 769775.CrossRefGoogle ScholarPubMed
Flyvbjerg, A., Frystyk, J., Thorlacius-Ussing, O. & Ørskov, H. (1989). Somatostatin analogue administration prevents increase in kidney somatomedin C and initial renal growth in diabetic and uninephrectomized rats. Diabetologia 32, 261265.CrossRefGoogle ScholarPubMed
Froesch, E. R., Schmid, C., Schwander, J. & Zapf, J. (1985). Actions of insulin-like growth factors. Annual Reviews of Physiology 47, 443467.CrossRefGoogle ScholarPubMed
George, G. A. & Heaton, F. W. (1978). Effect of magnesium deficiency on energy metabolism and protein synthesis by liver. International Journal of Biochemistry 9, 421425.CrossRefGoogle ScholarPubMed
Giugliano, R. & Millward, D. J. (1984). The effects of severe zinc deficiency on protein turnover in muscle and thymus. British Journal of Nutrition 52, 545560.CrossRefGoogle Scholar
Golden, M. H. N. (1988). The role of individual deficiencies in growth retardation of children as exemplified by zinc and protein. In Linear Growth Retardation in Less Developed Countries. Nestlé Nutrition Workshop Series, vol. 14. [Waterlow, J. C., editor]. Vevey: Nestec Ltd/New York: Raven Press.Google Scholar
Handelsman, D. J., Spaliviero, J. A., Scott, C. D. & Baxter, R. C. (1987). Hormonal regulation of the peripheral surge of insulin-like growth factor I in the rat. Endocrinology 120, 491496.CrossRefGoogle Scholar
Hunt, B. J. (1971). Age and magnesium deficiency in the rat with emphasis on bone and muscle magnesium. American Journal of Physiology 221, 18091817.CrossRefGoogle Scholar
Hurley, L. S. (1969). Zinc deficiency in the developing rat. American Journal of Clinical Nutrition 22, 13321339.CrossRefGoogle ScholarPubMed
Isley, W. L., Underwood, L. E. & Clemmons, D. R. (1983). Dietary components that regulate serum somatomedin-C concentrations in human. Journal of Clinical Investigation 71, 175182.CrossRefGoogle Scholar
Laditan, A. A. O. & Ette, S. I. (1982). Plasma zinc and copper levels during the acute phase of protein-energy malnutrition (PEM) and after recovery. Tropical and Geographical Medicine 34, 7780.Google ScholarPubMed
Miller, W. J. (1969). Absorption, tissue distribution, endogenous excretion, and homeostatic control of zinc in ruminants. American Journal of Clinical Nutrition 22, 13231331.CrossRefGoogle ScholarPubMed
O'Leary, M. J., McClain, C. J. & Hegarty, P. V. J. (1979). Effect of zinc deficiency on the weight, cellularity and zinc concentration of different skeletal muscles in the post-weanling rat. British Journal of Nutrition 42, 487495.CrossRefGoogle ScholarPubMed
Öner, G., Bhaumick, B. & Bala, M. (1984). Effect of zinc deficiency on serum somatomedin levels and skeletal growth in young rats. Endocrinology 114, 18601863.CrossRefGoogle ScholarPubMed
Ørskov, H. & Seyer-Hansen, K. (1974). Measurement of and correction for incubation damage in radioimmunoassay. European Journal of Clinical Investigation 4, 207211.CrossRefGoogle ScholarPubMed
Ørskov, H., Thomsen, A. G. & Yde, H. (1968). Wick-chromatography for rapid and reliable immunoassay of insulin, glucagon and growth hormone. Nature 219, 193195.CrossRefGoogle ScholarPubMed
Pitts, G. C. (1986). Cellular aspects of growth and catch-up growth in the rat: a reevaluation. Growth 50, 419436.Google Scholar
Prasad, A. S., Oberlease, D., Wolf, P. & Horwitz, T. J. (1969). Effect of growth hormone on non-hypophyseetomized zinc-deficient rats. Journal of Laboratory and Clinical Medicine 73, 486494.Google ScholarPubMed
Schwander, J. C., Hauri, C., Zapf, J. & Froesch, E. R. (1983). Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: Dependence on growth hormone status. Endocrinology 113, 297305.CrossRefGoogle ScholarPubMed
Schwartz, R., Woodcock, N. A., Blakely, J. D., Wang, F. L. & Khairallah, E. A. (1970). Effect of magnesium deficiency in growing rats on synthesis of liver proteins and serum albumin. Journal of Nutrition 100, 123128.CrossRefGoogle ScholarPubMed
Smith, F. I., Taiwo, O. & Payne-Robinson, H. M. (1989). Plasma somatomedin C in Nigerian malnourished children fed a vegetable protein rehabilitation diet. European Journal of Clinical Nutrition 43, 705713.Google ScholarPubMed
Southon, S., Livesey, G., Gee, J. M. & Johnson, I. T. (1985). Intestinal cellular proliferation and protein synthesis in zinc-deficient rats. British Journal of Nutrition 53, 595603.CrossRefGoogle ScholarPubMed
Takahashi, K., Daughaday, W. H. & Kipnis, D. M. (1971). Regulation of immunoreactive growth hormone secretion in male rats. Endocrinology 88, 909917.CrossRefGoogle ScholarPubMed
Warner, R. G. & Breuer, L. H. (1972). Nutrient requirements of the laboratory rat. In Nutrient Requirements of Laboratory Animals, 2nd ed., pp. 5695. Washington, DC: National Academy of Sciences.Google Scholar
Wilkins, P. J., Grey, P. C. & Dreosti, I. E. (1972). Plasma zinc as an indicator of zinc status in rats. British Journal of Nutrition 27, 113120.CrossRefGoogle ScholarPubMed
Williams, R. B. & Mills, C. F. (1970). The experimental production of zinc deficiency in the rat. British Journal of Nutrition 24, 9891003.CrossRefGoogle ScholarPubMed
Winick, M. & Noble, A. (1966). Cellular response in rats during malnutrition at various ages. Journal of Nutrition 89, 300306.CrossRefGoogle ScholarPubMed