REDUCED LIVER INSULIN-LIKE GROWTH-FACTOR-I GENE-EXPRESSION IN YOUNG ZINC-DEPRIVED RATS IS ASSOCIATED WITH A DECREASE IN LIVER GROWTH-HORMONE (GH) RECEPTORS AND SERUM GH-BINDING PROTEIN

Zinc depletion attenuates growth and decreases circulating IGF-I. To i nvestigate the mechanisms responsible for the IGF-I decline, we determ ined the effects of dietary zinc (Zn) deficiency on body and organ gro wth, serum IGF-I, serum GH-binding protein (GHBP), liver GH receptors and liver expression of their corresponding gene. After 1 week of adap tation to a normal zinc diet, a zinc-deficient diet (ZD; Zn, 0 p.p.m.) or a zinc-normal diet (CTR; Zn, 75 p.p.m.) was available an libitum t o 4-week-old Wistar rats for 4 weeks. Pair-fed animals (PF) received t he zinc-normal diet in the same absolute amount as that consumed the d ay before by the ZD group. The food intake of ZD and PF rats was reduc ed by 32% (P<0.001) compared with the CTR group. Zinc depletion specif ically reduced body weight gain (-22%, P<0.05), serum IGF-I concentrat ions (-52%, P<0.001), hepatic GH receptors (-28%; P<0.05) and serum GH BP levels (-51%; P<0.05), compared with the PF group. GH concentration s were reduced in ZD animals compared with CTR rats (P<0.01). The calo ric restriction of PF animals also decreased body weight gain (-50%, P <0.001), serum IGF-I concentrations (-21%, P<0.05), liver GH receptors (-38%, P<0.001) and serum GHBP levels (-38%, P<0.01), when compared w ith the CTR group. Both ZD and PF groups had reduced liver IGF-I and G H receptor/GHBP mRNA levels in comparison with the CTR group (P<0.01). However, only liver IGF-I mRNA levels were specifically reduced by zi nc deficiency (ZD vs PF rats; P<0.05). Our observations suggest that b eside the decline of GH secretion, decreased hepatic GH receptors and/ or GHBP concentrations might be responsible for the decline of circula ting TGF-I in ZD animals.