The impaired growth induced by zinc deficiency in rats is associated with decreased expression of the hepatic insulin-like growth factor I and growth hormone receptor genes

This study was conducted to determine whether dietary zinc status affects the expression of the insulin-like growth factor I and growth hormone receptor/growth hormone binding protein genes in the liver of growing rats. Weanling male Sprague-Dawley rats were randomly allotted to zinc-deficient, pair-fed or ad libitum-fed dietary treatments and fed diets containing no added zinc for 14 d. Zinc acetate was added to the deionized, distilled water (30 mg/L) provided to pair-fed and ad libitum-fed rats. As expected, zinc deficiency significantly reduced growth rate by 60% and was associated with a significantly lower serum insulin-like growth factor I concentration (46 and 67% lower than pair-fed and ad libitum-fed rats, respectively). The reduction in serum insulin-like growth factor I concentration was associated with a decrease in insulin-like growth factor I gene expression. The abundance of the 7.5-kb insulin-like growth factor I mRNA transcript in zinc-deficient and pair-fed rats was 14 and 31% that of the ad libitum-fed rats. The 0.8-1.2-kb insulin-like growth factor I transcript also was significantly lower in the zinc-deficient and pair-fed rats. In contrast, the abundance of the 1.8-kb insulin-like growth factor I transcript was unaffected by zinc deficiency. The growth hormone receptor mRNA levels of zinc-deficient and pair-fed rats were 17 and 50% and their growth hormone binding protein mRNA levels were 46 and 65% those of the ad libitum-fed rats. In summary, zinc deficiency markedly decreases expression of the insulin-like growth factor I and growth hormone receptor genes. The mechanisms that account for the decreases are obscure. Nonetheless, our results indicate that the growth retardation caused by zinc deficiency is associated with defects in the growth hormone receptor signaling pathway.