Transcriptional regulation of episodic glucocorticoid secretion

Transcriptional regulation of episodic glucocorticoid secretion
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DOI:
10.1016/j.mce.2012.10.011
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发表时间:
2013-05-22
影响因子:
4.1
通讯作者:
Aguilera, Greti
Aguilera, Greti
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Ying;Smith, Lorna I.;Aguilera, Greti

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昼夜节律和超昼夜变化的基础糖皮质激素分泌和短暂的升高,在压力是必不可少的稳态。使用内含子qRT-PCR来测量初级转录物(hnRNA)的变化,我们已经表明,由应激或ACTH注射诱导的分泌事件之后是速率限制性类固醇生成蛋白质(例如类固醇生成急性调节蛋白(星星)、细胞色素P450侧链裂解和黑皮质素受体相关蛋白)转录的偶发性增加。这些转录事件意味着类固醇生成蛋白的快速周转和每个分泌事件后的新合成的需要。除了偶发性ACTH分泌外,肾上腺束水平的细胞内反馈机制可能有助于转录事件的产生。CREB共激活子、调节CREB活性的转导子(TORC)在转录事件之前活化和易位至细胞核之间的时间关系表明TORC参与星星和其他类固醇生成蛋白的转录活化。出版社:Elsevier爱尔兰Ltd.
Circadian and ultradian variations of basal glucocorticoid secretion and transient elevations during stress are essential for homeostasis. Using intronic qRT-PCR to measure changes in primary transcript (hnRNA) we have shown that secretory events induced by stress or ACTH injection are followed by episodic increases in transcription of rate limiting steroidogenic proteins, such as steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage and melanocortin receptor associated protein. These transcriptional episodes imply rapid turnover of steroidogenic proteins and the need of de nova synthesis following each secretory event. In addition to episodic ACTH secretion, it is likely that intracellular feedback mechanisms at the adrenal fasciculata level contribute to the generation of episodes of transcription. The time relationship between activation and translocation of the CREB co-activator, transducer of regulated CREB activity (TORC) to the nucleus preceding transcriptional episodes suggest the involvement of TORC in the transcriptional activation of StAR and other steroidogenic proteins. Published by Elsevier Ireland Ltd.