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 affe cts the expression of the insulin-like growth factor I and growth horm one receptor/growth hormone binding protein genes in the liver of grow ing 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 libi tum-fed rats. As expected, zinc deficiency significantly reduced growt h rate by 60% and was associated with a significantly lower serum insu lin-like growth factor I concentration (46 and 67% lower than pair-fed and ad libitum-fed rats, respectively). The reduction in serum insuli n-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 an d 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 significantl y lower in the zinc-deficient and pair-fed rats. In contrast, the abun dance of the 1.8-kb insulin-like growth factor I transcript was unaffe cted by zinc deficiency. The growth hormone receptor mRNA levels of zi nc-deficient and pair-fed rats were 17 and 50% and their growth hormon e 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. T he mechanisms that account for the decreases are obscure. Nonetheless, our results indicate that the growth retardation caused by zinc defic iency is associated with defects in the growth hormone receptor signal ing pathway.