Failure of exogenous IGF-I to restore normal growth in rats submitted to dietary zinc deprivation.
Dietary zinc deficiency in rats causes growth retardation associated with decreased circulating IGF-I concentrations. To investigate the potential role of low IGF-I in this condition, we attempted to reverse the growth failure by administration of exogenous IGF-I. Rats were fed for 4 weeks a zinc-deficient diet (ZD, Zn 0 ppm) or were pair-fed a zinc-normal diet (PF, Zn 75 ppm). We compared the anabolic action of recombinant human (rh) IGF-I infused at the dose of 120 microg/day for the last experimental week in ZD, PF and freely fed control (CTRL) rats. Zinc 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% of PF; P<0. 01). While exogenous IGF-I increased body weight in CTRL (+12 g; P<0. 01) and PF (+7 g; not significant) animals, growth was not stimulated in ZD rats (-1.5 g) in comparison with the corresponding untreated groups. However, circulating IGF-I and IGFBP-3 levels were restored by IGF-I infusion to levels similar to those in untreated CTRL rats. In conclusion, restoration of normal circulating levels of IGF-I and IGFBP-3 by rhIGF-I infusion fails to reverse the growth retardation induced by zinc deficiency. These results suggest that growth retardation 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.
Ninh
N X
NX
Diabetes and Nutrition Unit, School of Medicine, Catholic University of Louvain, B-1200 Brussels, Belgium.
Maiter
D
D
Verniers
J
J
Lause
P
P
Ketelslegers
J M
JM
Thissen
J P
JP
D000704:Analysis of Variance; D000818:Animals; D004032:Diet; D004435:Eating; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D017211:Treatment Failure; D015430:Weight Gain / Q000187:drug effects; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency*
D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D015032:Zinc