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 insulin-like growth factor-I (IGF-I). To determine whether the low circulating IGF-I concentrations are responsible for the stunted growth, the growth response of zinc-deficient hypophysectomized rats to supplementation with recombinant human IGF-I (hIGF-I) was investigated. There were three dietary groups: 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 received hIGF-I (150 micrograms/day) by subcutaneous infusion for 12 days, except for half of the animals in the control group which were sham-treated and which received vehicle infusion for the same period of time. The magnitude of the change was small, nevertheless infusion of hIGF-I significantly increased (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 lack of zinc in the diet, as evidenced by continuous weight loss, no increase in tail length and lowered tibial epiphyseal width in zinc-deficient animals. We conclude that systemic supplementation of hIGF-I can promote growth in hypophysectomized rats. The absence of weight gain and bone growth in zinc-deficient animals during the infusion period suggests that the growth promoting effect of circulating IGF-I is impaired by zinc deficiency.