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

in Journal of Endocrinology
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N X Ninh
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J-P Thissen
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D Maiter
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E Adam
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N Mulumba
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J-M Ketelslegers
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Abstract

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). However, only liver IGF-I mRNA levels were specifically reduced by zinc deficiency (ZD vs PF rats; P<0·05). Our observations suggest that beside the decline of GH secretion, decreased hepatic GH receptors and/or GHBP concentrations might be responsible for the decline of circulating IGF-I in ZD animals.

Journal of Endocrinology (1995) 144, 449–456

 

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