Exploring hepatic hormone actions using a compilation of gene expression profiles.
Exploring hepatic hormone actions using a compilation of gene expression profiles.
复制标题
DOI：
10.1186/1472-6793-5-8
复制
发表时间：
2005-06-13
期刊：
影响因子：
--
通讯作者：
Flores-Morales, Amilcar
中科院分区：
文献类型：
--
作者：
Stahlberg, Nina;Merino, Roxana;Flores-Morales, Amilcar
背景技术背景：微阵列分析在内分泌研究领域内是有吸引力的，因为基因表达的调节是激素发挥其作用的关键机制。基于信息丰富的表达谱的知识发现和假设检验有望加速生理相关激素作用机制的发现。然而，迄今为止，大多数研究集中在单个激素的作用的分析和存在的例子很少，试图使用不同的激素调节的表达谱的汇编，以获得洞察激素如何作用，以调节组织生理。本报告说明了如何从一个单一的组织，肝脏获得的多个转录本配置文件的荟萃分析，可用于评估相关的假设，并发现新的激素作用机制。我们已经评估了生长激素（GH）和雌激素在肝脏性别差异基因表达的调节以及参与的甾醇调节元件结合蛋白（SREBPs）在GH和甲状腺激素的肝脏actions.RESULTS：小相似性之间存在的差异肝转录谱由17-α-乙炔基炔雌醇和bGH的连续输注引起的。另一方面，强相关性被发现之间的两个配置文件和女性丰富的转录谱。因此，雌激素在雄性大鼠肝脏中具有不同于GH的雌性化作用。bGH和T3之间的相似性仅限于一小组基因，其中大多数涉及脂肪生成。对甲状腺激素快速调节的基因的计算机启动子分析预测了短期体内治疗对SREBPs的激活。它进一步表明，内质网中的SREBP 1的蛋白水解加工可能有助于T3对这些基因的快速行动。结论：本报告说明了多个转录本配置文件的荟萃分析可以用来连接有关内分泌生理学的知识在基因表达的变化，以nervally-induced。我们得出结论，生长激素和雌激素是重要的决定因素，性别相关的差异，肝脏基因表达。快速的肝甲状腺激素效应可能通过诱导SREBP 1蛋白水解加工影响参与脂肪生成的基因。
BACKGROUND: Microarray analysis is attractive within the field of endocrine research because regulation of gene expression is a key mechanism whereby hormones exert their actions. Knowledge discovery and testing of hypothesis based on information-rich expression profiles promise to accelerate discovery of physiologically relevant hormonal mechanisms of action. However, most studies so-far concentrate on the analysis of actions of single hormones and few examples exist that attempt to use compilation of different hormone-regulated expression profiles to gain insight into how hormone act to regulate tissue physiology. This report illustrates how a meta-analysis of multiple transcript profiles obtained from a single tissue, the liver, can be used to evaluate relevant hypothesis and discover novel mechanisms of hormonal action. We have evaluated the differential effects of Growth Hormone (GH) and estrogen in the regulation of hepatic gender differentiated gene expression as well as the involvement of sterol regulatory element-binding proteins (SREBPs) in the hepatic actions of GH and thyroid hormone.RESULTS: Little similarity exists between liver transcript profiles regulated by 17-alpha-ethinylestradiol and those induced by the continuos infusion of bGH. On the other hand, strong correlations were found between both profiles and the female enriched transcript profile. Therefore, estrogens have feminizing effects in male rat liver which are different from those induced by GH. The similarity between bGH and T3 were limited to a small group of genes, most of which are involved in lipogenesis. An in silico promoter analysis of genes rapidly regulated by thyroid hormone predicted the activation of SREBPs by short-term treatment in vivo. It was further demonstrated that proteolytic processing of SREBP1 in the endoplasmic reticulum might contribute to the rapid actions of T3 on these genes.CONCLUSION: This report illustrates how a meta-analysis of multiple transcript profiles can be used to link knowledge concerning endocrine physiology to hormonally induced changes in gene expression. We conclude that both GH and estrogen are important determinants of gender-related differences in hepatic gene expression. Rapid hepatic thyroid hormone effects affect genes involved in lipogenesis possibly through the induction of SREBP1 proteolytic processing.