FAILURE OF EXOGENOUS IGF-I TO RESTORE NORMAL GROWTH IN RATS SUBMITTEDTO DIETARY ZINC DEPRIVATION

Dietary zinc deficiency in rats causes growth retardation associated w ith decreased circulating IGF-I concentrations. To investigate the pot ential role of low IGF-I in this condition, we attempted to reverse th e growth failure by administration of exogenous IGF-I. Rats were fed f or 4 weeks a zinc-deficient diet (ZD, Zn 0 ppm) or were pair-fed a zin c-normal diet (PF, Zn 75 ppm). We compared the anabolic action of reco mbinant human (rh) IGF-I infused at the dose of 120 mu g/day for the l ast experimental week in ZD, PF and freely fed control (CTRL) rats. Zi nc deficiency caused growth stunting (weight gain 47% of PF; P<0.001), decreased circulating IGF-I (52% of PF; P<0.01) and liver IGF-I mRNA (67% of PF: P<0.01). Serum insulin-like growth factor-binding protein- 3 (IGFBP-3) assessed by ligand blot was also reduced in ZD rats (65% o f PF; P<0.01). While exogenous IGF-I increased body weight in CTRL (+1 2 g; P<0.01) and PF (+7 g; not significant) animals, growth was not st imulated in ZD rats (- 1.5 g) in comparison with the corresponding unt reated groups. However, circulating IGF-I and IGFBP-3 levels were rest ored by IGF-I infusion to levels similar to those in untreated CTRL ra ts. In conclusion, restoration of normal circulating levels of IGF-I a nd IGFBP-3 by rhIGF-I infusion fails to reverse the growth retardation induced by zinc deficiency. These results suggest that growth retarda tion related to zinc deficiency is not only caused by low serum IGF-I concentrations, but also by inhibition of the anabolic actions of IGF- I.