Failure of IGF-I infusion to promote growth in Zn deficient hypophysectomized rats

The retarded growth of zinc-deficient rats is associated with low plasma in sulin-like growth factor-I (IGF-I). To determine whether the low circulatin g IGF-I concentrations are responsible for the stunted growth, the growth r esponse of zinc-deficient hypophysectomized rats to supplementation with re combinant human IGF-I (hIGF-I) was investigated. There were three dietary g roups: zinc-deficient (0.9 mg zinc/kg diet), controls (66 mg zinc/kg diet) and zinc-adequate pair-fed (66 mg zinc/kg diet). All rats in each group rec eived hIGF-I (150 mu g/day) by subcutaneous infusion for 12 days, except fo r half of the animals in the control group which were sham-treated and whic h received vehicle infusion for the same period of time. The magnitude of t he change was small, nevertheless infusion of hIGF-I significantly increase d (p<0.05) the body weight, tail length, liver weight and tibial epiphyseal width of control animals. This growth effect of hIGF-I was inhibited by la ck of zinc in the diet, as evidenced by continuous weight loss, no increase in tail length and lowered tibial epiphyseal width in zinc-deficient anima ls. We conclude that systemic supplementation of hIGF-I can promote growth in hypophysectomized rats. The absence of weight gain and bone growth in zi nc-deficient animals during the infusion period suggests that the growth pr omoting effect of circulating IGF-I is impaired by zinc deficiency.