Large-scale analysis of glucocorticoid target genes in rat hypothalamus
Large-scale analysis of glucocorticoid target genes in rat hypothalamus
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DOI：
10.1111/j.1471-4159.2008.05489.x
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发表时间：
2008-07-01
影响因子：
4.7
通讯作者：
Mikuni, M.
中科院分区：
文献类型：
--
作者：
Sato, H.;Horikawa, Y.;Mikuni, M.
糖皮质激素（GC）信号传导不足在重度抑郁症（MDD）中经常被观察到。由于情绪和行为症状通常伴随着下丘脑系统的紊乱，该区域的GC不足被认为是MDD发病机制中的重要因素。在这项研究中，22个早期GC反应基因，包括15个上调和7个下调的基因在大鼠下丘脑被确定为受到地塞米松至少两倍的调控，使用微阵列与22 599个独特的转录本。在这22个基因中，其中5个是新的GC响应基因，在体外的表达模式的sgk，bcl 6，pdk 4，和plekhf 1进行了详细的检查，和GC响应区域内的sgk启动子被确定。这表明，糖皮质激素反应元件独立的途径也发挥了关键作用，在下丘脑早期GC反应。考虑到这些GC反应基因中的一些是候选的神经元调节因子，该基因列表应该有助于澄清GC不足和MDD发病机制之间的关系。
Insufficient glucocorticoid (GC) signaling is frequently observed in major depressive disorder (MDD). Since emotional and behavioral symptoms are often accompanied by disturbances in hypothalamic systems, GC insufficiency in this region is regarded as important in the pathogenesis of MDD. In this study, 22 early GC-responsive genes comprising 15 up-regulated and 7 down-regulated genes in rat hypothalamus were identified as being regulated at least two-fold by dexamethasone using microarray with 22 599 unique transcripts. Among these 22 genes, five of which are novel GC-responsive genes, the expression patterns of sgk, bcl6, pdk4, and plekhf1 were examined in vitro in detail, and GC-responsive regions were identified only within the promoter of sgk. This suggests that glucocorticoid response element-independent pathways also play a critical role in early GC-response in hypothalamus. Considering that a number of these GC-responsive genes are candidate neuronal regulators, this gene list should be useful in clarifying the relationship between GC insufficiency and the pathogenesis of MDD.