The significance of glucocorticoid pulsatility

被引:173
作者
Lightman, Stafford L. [1 ]
Wiles, Crispin C. [1 ]
Atkinson, Helen C. [1 ]
Henley, David E. [1 ]
Russell, Georgina M. [1 ]
Leendertz, Jack A. [1 ]
McKenna, Mervyn A. [1 ]
Spiga, Francesca [1 ]
Wood, Susan A. [1 ]
Conway-Campbell, Becky L. [1 ]
机构
[1] Univ Bristol, Henry Wellcome Labs Integrative Neurosci & Endocr, Bristol BS1 3NY, Avon, England
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
glucocorticoid receptor; mineralocorticoid receptor; proteasome; ultradian rhythm;
D O I
10.1016/j.ejphar.2007.11.073
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Glucocorticoids are secreted in discrete pulses resulting in an ultradian rhythm in all species that have been studied. In the rat there is an approximately hourly rhythm of corticosterone secretion, which appears to be regulated by alternating activation and inhibition of the HPA axis. At the level of signal transduction, the response to these pulses of corticosterone is determined by its dynamic interaction with the two transcription factors - the glucocorticoid and mineralocorticoid receptors. While the mineralocorticoid receptor remains activated throughout the ultradian cycle, the glucocorticoid receptor shows a phasic response to each individual pulse of corticosterone. This phasic response is regulated by an intranuclear proteasome-dependent rapid downregulation of the activated glucocorticoid receptor. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:255 / 262
页数:8
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