Beyond Synergy: Corticosterone and Thyroid Hormone Have Numerous Interaction Effects on Gene Regulation in Xenopus tropicalis Tadpoles
Beyond Synergy: Corticosterone and Thyroid Hormone Have Numerous Interaction Effects on Gene Regulation in Xenopus tropicalis Tadpoles
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DOI：
10.1210/en.2012-1432
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发表时间：
2012-11-01
期刊：
影响因子：
4.8
通讯作者：
Buchholz, Daniel R.
中科院分区：
文献类型：
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作者：
Kulkarni, Saurabh S.;Buchholz, Daniel R.
激素在脊椎动物的发育过程中起重要作用，青蛙变态是研究甲状腺激素和糖皮质激素在发育中作用的理想模型。TH调节变态的开始和速度，而皮质酮（CORT;青蛙中主要的糖皮质激素）的作用更为复杂。在变态前没有TH时，CORT抑制发育，但在变态时有TH存在时，CORT与TH协同促进发育。已知青蛙中三种基因在基因表达水平上的协同作用，但TH和CORT串扰的性质和程度尚不清楚。因此，为了研究TH和CORT的相互作用，我们对用CORT、TH、CORT+TH或溶剂处理18小时的热带爪蟾蝌蚪的尾巴进行了微阵列分析。5432个基因的表达显着改变，在响应一个或两个激素。使用维恩图和聚类分析，我们确定了16个主要的基因调控模式，由于TH和/或CORT的上调或下调。许多基因只受其中一种激素的影响，大部分受调控的基因（22%）需要两种激素。我们还确定了模式的添加剂或协同，抑制，消减和湮灭的监管。共有928个基因（17%）受到两种激素之间的新相互作用的调控。这些数据扩展了我们对激素串扰的理解，这些激素串扰是指导尾部吸收的基因调控级联反应的基础，并表明CORT不仅影响TH依赖性组织转化的时间，而且影响TH依赖性组织转化的性质。（内分泌学153：5309-5324，2012）
Hormones play critical roles in vertebrate development, and frog metamorphosis has been an excellent model system to study the developmental roles of thyroid hormone (TH) and glucocorticoids. Whereas TH regulates the initiation and rate of metamorphosis, the actions of corticosterone (CORT; the main glucocorticoid in frogs) are more complex. In the absence of TH during premetamorphosis, CORT inhibits development, but in the presence of TH during metamorphosis, CORT synergizes with TH to accelerate development. Synergy at the level of gene expression is known for three genes in frogs, but the nature and extent of TH and CORT cross talk is otherwise unknown. Therefore, to examine TH and CORT interactions, we performed microarray analysis on tails from Xenopus tropicalis tadpoles treated with CORT, TH, CORT+TH, or vehicle for 18 h. The expression of 5432 genes was significantly altered in response to either or both hormones. Using Venn diagrams and cluster analysis, we identified 16 main patterns of gene regulation due to upor down-regulation by TH and/or CORT. Many genes were affected by only one of the hormones, and a large proportion of regulated genes (22%) required both hormones. We also identified patterns of additive or synergistic, inhibitory, subtractive, and annihilatory regulation. A total of 928 genes (17%) were regulated by novel interactions between the two hormones. These data expand our understanding of the hormonal cross talk underlying the gene regulation cascade directing tail resorption and suggest the possibility that CORT affects not only the timing but also the nature of TH-dependent tissue transformation. (Endocrinology 153:5309-5324, 2012)