Zinc depletion attenuates growth and decreases circulating IGF-I. To investigate the mechanisms responsible for the IGF-I decline, we determined the effects of dietary zinc (Zn) deficiency on body and organ growth, serum IGF-I, serum GH-binding protein (GHBP), liver GH receptors and liver expression of their corresponding gene. After 1 week of adaptation 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 ad libitum to 4-week-old Wistar rats for 4 weeks. Pair-fed animals (PF) received the zinc-normal diet in the same absolute amount as that consumed the day before by the ZD group. The food intake of ZD and PF rats was reduced by 32% (P < 0.001) compared with the CTR group. Zinc depletion specifically reduced body weight gain (-22%, P < 0.05), serum IGF-I concentrations (-52%, P < 0.001), hepatic GH receptors (-28%; P < 0.05) and serum GHBP levels (-51%; P < 0.05), compared with the PF group. GH concentrations were reduced in ZD animals compared with CTR rats (P < 0.01). The caloric 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 with the CTR group. Both ZD and PF groups had reduced liver IGF-I and GH receptor/GHBP mRNA levels in comparison with the CTR group (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)