Role of insulin-like growth factor-1 and growth hormone in growth inhibition induced by magnesium and zinc deficiencies
Authors: Dørup Inge , Flyvbjerg Allan , Everts Maria E. , Clausen Torben 
Published: September 2005

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.