Ultradian glucocorticoid exposure directs gene-dependent and tissue-specific mRNA expression patterns in vivo

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:439

Article

George, Charlotte L.^1,2  Birnie, Matthew T.¹  Flynn, Benjamin P.¹  Kershaw, Yvonne M.¹  Lightman, Stafford L.¹  Conway-Campbell, Becky L.¹ 

[1] Univ Bristol, Sch Clin Sci, Henry Wellcome Labs Integrat Neurosci & Endocrino, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England

[2] Univ Oxford, MRC Weatherall Inst Mol Med, John Radcliffe Hosp, CGAT,Ctr Computat Biol, Oxford OX3 9DS, England

关键词: Ultradian rhythm;    Glucocorticoids;    GR;    Pituitary;    Prefrontal cortex;    Transcription;   

DOI  :  10.1016/j.mce.2016.10.019

来源: Elsevier

【 摘 要 】

In this paper we report differential decoding of the ultradian corticosterone signal by glucocorticoid target tissues. Pulsatile corticosterone replacement in adrenalectomised rats resulted in different dynamics of Sgk1 mRNA production, with a distinct pulsatile mRNA induction profile observed in the pituitary in contrast to a non-pulsatile induction in the prefrontal cortex (PFC). We further report the first evidence for pulsatile transcriptional repression of a glucocorticoid-target gene in vivo, with pulsatile regulation of Pomc transcription in pituitary. We have explored a potential mechanism for differences in the induction dynamics of the same transcript (Sgk1) between the PFC and pituitary. Glucocorticoid receptor (GR) activation profiles were strikingly different in pituitary and prefrontal cortex, with a significantly greater dynamic range and shorter duration of GR activity detected in the pituitary, consistent with the more pronounced gene pulsing effect observed. In the prefrontal cortex, expression of Gilz mRNA was also non-pulsatile and exhibited a significantly delayed timecourse of increase and decrease when compared to Sgk1, additionally highlighting gene-specific regulatory dynamics during ultradian glucocorticoid treatment. (C) 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license.

【 授权许可】

Free