Ethanol suppresses growth hormone-mediated cellular responses in liver slices.
Ethanol suppresses growth hormone-mediated cellular responses in liver slices.
复制标题
乙醇抑制肝切片中生长激素介导的细胞反应。
DOI：
10.1111/j.1530-0277.1995.tb01607.x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Sonntag,WE
中科院分区：
文献类型：
--
作者：
Xu,X;Ingram,RL;Sonntag,WE
先前的研究表明，急性和慢性乙醇摄入都会抑制蛋白质的合成，并减少胰岛素样生长因子-1(IGF-1)的分泌。虽然IGF-1的合成和分泌受到脑下垂体生长激素分泌的调节，但我们评估了乙醇是否抑制组织对生长激素的反应。取雄性SD大鼠肝切片，置于F-12培养液中，37℃下分别加入[~3H]亮氨酸、0.25或1 nM大鼠生长激素和0、37或175 mM乙醇(毒性水平)。分别于0、15、30、60min取出组织。在此期间，蛋白质合成呈线性增加，给予生长激素(1 NM)显著增加蛋白质合成速率48%(p<；0.01)，而添加37或175 mM乙醇则减弱生长激素的影响(p<；0.01)。对IGF-1mRNA的分析表明，生长激素的反应增加了2倍(p<；0.01)，而乙醇处理降低了生长激素诱导的IGF-1mRNA的升高。乙醇(175 MM)抑制IGF-1的释放(p<；0.05)。乙醇不改变生长激素受体的结合，组织切片暴露于乙醇也不影响生长激素受体的数量或生长激素与其受体的亲和力。结果表明：(1)生长激素是IGF-1mRNA和IGF-1肽释放的强烈急性调节器；(2)乙醇抑制生长激素诱导的蛋白质合成和IGF-1基因表达；(3)乙醇对生长激素的抑制作用不改变生长激素受体的数量或结合特性。我们得出结论，乙醇抑制生长激素诱导的信号转导，导致IGF-1基因表达下降。
Previous studies indicate that both acute and chronic ethanol administration 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°C with [3H]leucine, and either 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 protein synthetic rate by 48% (p< 0.01), whereas addition of 37 or 175 mM ethanol attenuated the effects of growth hormone (p< 0.01). Analysis of IGF‐1 mRNA indicated a 2‐fold increase in response to growth hormone (p< 0.01), whereas ethanol administration decreased the growth hormone‐induced rise of IGF‐1 mRNA. Ethanol (175 mM) inhibited the release 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) growth hormone is a potent acute regulator of IGF‐1 mRNA and IGF‐1 peptide release, (2) ethanol inhibits growth hormone‐induced protein synthesis and induction of IGF‐1 gene expression, and (3) the inhibitory effects of ethanol on growth hormone occur without changing growth hormone receptor number or binding characteristics. We conclude that ethanol suppresses growth hormone‐induced signal transduction, resulting in a decrease in IGF‐1 gene expression.