Histone deacetylase 1 (HDAC1) participates in the down-regulation of corticotropin releasing hormone gene (crh) expression.
Histone deacetylase 1 (HDAC1) participates in the down-regulation of corticotropin releasing hormone gene (crh) expression.
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DOI：
10.1016/j.physbeh.2011.03.026
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发表时间：
2011-08-03
影响因子：
2.9
通讯作者：
Uht, Rosalie M.
中科院分区：
文献类型：
--
作者：
Miller, Lydia;Foradori, Chad D.;Lalmansingh, Avin S.;Sharma, Dharmendra;Handa, Robert J.;Uht, Rosalie M.
下丘脑室旁核(PVH)在调节下丘脑-垂体-肾上腺(HPA)轴中起着中枢作用。PVH的内侧小细胞神经元(MpPVH)整合感觉和体液输入以维持内稳态。体液输入包括由肾上腺分泌的糖皮质激素，它下调HPA的激活。糖皮质激素的主要靶点是合成和分泌促肾上腺皮质激素释放因子的mpPVH神经元群体，其中最有效的是促肾上腺皮质激素释放激素(CRH)。虽然已知CRH基因(CRH)的表达受糖皮质激素的下调，但这一过程发生的机制仍不清楚。开始这项研究时，我们假设糖皮质激素抑制CRH涉及到CRH近端启动子区域的HDAC募集。为了评估这一假设，我们用HDAC抑制剂曲古抑素A(TSA)处理了表达CRH的下丘脑细胞。正如预测的那样，TSA治疗导致CRH mRNA水平和CRH启动子活性增加。虽然与地塞米松(10−7 M)共处理可降低TSA对基因表达水平的影响，但不能降低启动子活性，但共转染HDAC1而不是3可恢复对地塞米松的抑制作用。在CRH启动子占有率方面，HDAC1和HDAC3之间的差异也很明显。Dex导致HDAC1占用率增加，但HDAC3占用率没有增加。体内研究表明，CRH免疫反应阳性(-ir)神经元含有HDAC1和HDAC3-ir。总而言之，这些数据表明HDAC1在CRH的生理调节中发挥了作用。
The paraventricular nucleus of the hypothalamus (PVH) plays a central role in regulating the hypothalamic-pituitary-adrenal (HPA) axis. Medial parvocellular neurons of the PVH (mpPVH) integrate sensory and humoral inputs to maintain homeostasis. Humeral inputs include glucocorticoids secreted by the adrenals, which down-regulate HPA activation. A primary glucocorticoid target is the population of mpPVH neurons that synthesize and secrete corticotropin-releasing factors, the most potent of which is corticotropin-releasing hormone (CRH). Although CRH gene (crh) expression is known to be down-regulated by glucocorticoids, the mechanisms by which this process occurs are still poorly understood. To begin this study we postulated that glucocorticoid repression of crh involves HDAC recruitment to the region of the crh proximal promoter. To evaluate this hypothesis, we treated hypothalamic cells that express CRH with the HDAC inhibitor trichostatin A (TSA). As predicted, treatment with TSA led to increased CRH mRNA levels and crh promoter activity. Although co-treatment with Dex (10−7 M) reduced the TSA effect on mRNA levels, it failed to reduce promoter activity; however co-transfection of HDAC1 but not 3 restored Dex inhibition. A distinction between HDAC1 and 3 was also apparent with respect to crh promoter occupancy. Dex led to increased HDAC1 but not HDAC3 occupancy. In vivo studies revealed that CRH-immunoreactive (-ir) neurons contained HDAC1- and HDAC3-ir. Collectively, these data point to a role for HDAC1 in the physiologic regulation of crh.
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影响因子：
21.3
作者：
Stavreva DA;Wiench M;John S;Conway-Campbell BL;McKenna MA;Pooley JR;Johnson TA;Voss TC;Lightman SL;Hager GL
通讯作者：
Hager GL
影响因子：
5.3
作者：
Guenther, MG;Barak, O;Lazar, MA
通讯作者：
Lazar, MA
影响因子：
4.8
作者：
Chakrabarti, SK;James, JC;Mirmira, RG
通讯作者：
Mirmira, RG
影响因子：
25
作者：
Elliott, Evan;Ezra-Nevo, Gili;Chen, Alon
通讯作者：
Chen, Alon
影响因子：
3.2
作者：
Liu, Y;Kalintchenko, N;Aguilera, G
通讯作者：
Aguilera, G