Effect of ethanol on the synthesis of insulin-like growth factor 1 (IGF-1) and the IGF-1 receptor in late prepubertal female rats: a correlation with serum IGF-1.
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For several years, it has been well accepted that insulin-like growth factor 1 (IGF-1) plays a critical role in peripubertal growth. Recently, we have provided evidence to suggest that this peptide may also be involved in the sexual maturation process, via an action to stimulate hypothalamic luteinizing hormone releasing hormone release. Because ethanol (ETOH) delays puberty, an event that is associated with depressed growth rates and decreased growth hormone and luteinizing hormone (LH) secretion via actions at the hypothalamic level, we investigated whether this drug is capable of altering the expression of genes encoding IGF-1 in liver and brain, as well as the expression of the type 1 IGF receptor (IGF-1R) within the median eminence (ME). Also, we wanted to determine if any regional changes in the expression of these genes were associated with concomitant alterations in the serum levels of IGF-1 and LH. Rats were implanted with gastric cannulae on day 24 and began receiving specific control or ETOH diets on day 29. Rats were killed on day 34, determined to be in the late juvenile stage of development, and their tissues and blood were collected. Results indicate that the ETOH-fed rats showed a decrease (p < 0.01) in the expression of hepatic IGF-1 mRNA when compared with the controls, and this paralleled depressions in both serum IGF-1 (p < 0.01) and LH (p < 0.01). In contrast, no changes were detected in IGF-1 mRNA expression in the preoptic area and hypothalamus, as well as in IGF-1R mRNA expression within the ME. These results suggest that the well-known detrimental effects of ETOH on growth rates and the progression of the female pubertal process in the rat may be associated with the drug's ability to depress the hepatic synthesis of IGF-1 and the subsequent prepubertal circulating levels of the protein.
