ETHANOL SUPPRESSES GROWTH HORMONE-MEDIATED CELLULAR-RESPONSES IN LIVER SLICES

Previous studies indicate that both acute and chronic ethanol administ ration inhibit protein synthesis and decrease the secretion of insulin -like growth factor-1 (IGF-1). Although IGF-1 synthesis and secretion are regulated by growth hormone secretion from the pituitary gland, we assessed whether ethanol inhibits tissue response to growth hormone. Liver slices from male Sprague-Dawley rats were prepared, placed into F-12 media, and incubated at 37 degrees C with [H-3]leucine, and eithe r 0.25 or 1 nM rat growth hormone and 0, 37 (physiological levels), or 175 mM (toxic levels) ethanol. Tissues were removed at 0, 15, 30, and 60 min. protein synthesis increased linearly during this time period, and administration of growth hormone (1 nM) significantly increased p rotein synthetic rate by 48% (p < 0.01), whereas addition of 37 or 175 mM ethanol attenuated the effects of growth hormone (p < 0.01). Analy sis of IGF-1 mRNA indicated a 2-fold increase in response to growth ho rmone (p < 0.01), whereas ethanol administration decreased the growth hormone-induced rise of IGF-1 mRNA. Ethanol (175 mM) inhibited the rel ease of IGF-1 into the media (p < 0.05). Ethanol did not alter growth hormone receptor binding, and exposure of tissue slices to ethanol did not influence the number of growth hormone receptors or the affinity of growth hormone for its receptor. Our results demonstrate that (1) g rowth hormone is a potent acute regulator of IGF-1 mRNA and IGF-1 pept ide release, (2) ethanol inhibits growth hormone-induced protein synth esis and induction of IGF-1 gene expression, and (3) the inhibitory ef fects of ethanol on growth hormone occur without changing growth hormo ne receptor number or binding characteristics. We conclude that ethano l suppresses growth hormone-induced signal transduction, resulting in a decrease in IGF-1 gene expression.