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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Ultradian cortisol pulsatility encodes a distinct, biologically important signal
PLoS ONE, Volume 6, No. 1, Article e15766, Year 2011
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Description
Context: Cortisol is released in ultradian pulses. The biological relevance of the resulting fluctuating cortisol concentration has not been explored. Objective: Determination of the biological consequences of ultradian cortisol pulsatility. Design: A novel flow through cell culture system was developed to deliver ultradian pulsed or continuous cortisol to cells. The effects of cortisol dynamics on cell proliferation and survival, and on gene expression were determined. In addition, effects on glucocorticoid receptor (GR) expression levels and phosphorylation, as a potential mediator, were measured. Results: Pulsatile cortisol caused a significant reduction in cell survival compared to continuous exposure of the same cumulative dose, due to increased apoptosis. Comprehensive analysis of the transcriptome response by microarray identified genes with a differential response to pulsatile versus continuous glucocorticoid delivery. These were confirmed with qRT-PCR. Several transcription factor binding sites were enriched in these differentially regulated target genes, including CCAAT-displacement protein (CDP). A CDP regulated reporter gene (MMTV-luc) was, as predicted, also differentially regulated by pulsatile compared to continuous cortisol delivery. Importantly there was no effect of cortisol delivery kinetics on either GR expression, or activation (GR phosphoSer211). Conclusions: Cortisol oscillations exert important effects on target cell gene expression, and phenotype. This is not due to differences in cumulative cortisol exposure, or either expression, or activation of the GR. This suggests a novel means to regulate GR function. © 2011 Mosch et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3022879/bin/pone.0015766.s001.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3022879/bin/pone.0015766.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3022879/bin/pone.0015766.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3022879/bin/pone.0015766.s004.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3022879/bin/pone.0015766.s005.tif
Authors & Co-Authors
McMaster, Andrew
United Kingdom, Manchester
The University of Manchester
Jangani, Maryam
United Kingdom, Manchester
The University of Manchester
Sommer, Paula
United Kingdom, Manchester
The University of Manchester
South Africa, Durban
University of Kwazulu-natal
Han, Namshik
United Kingdom, Manchester
The University of Manchester
Brass, A.
United Kingdom, Manchester
The University of Manchester
Beesley, Stephen
United Kingdom, Manchester
The University of Manchester
Lu, Weiqun
United Kingdom, Manchester
The University of Manchester
Berry, Andrew
United Kingdom, Manchester
The University of Manchester
Loudon, Andrew
United Kingdom, Manchester
The University of Manchester
Donn, Rachelle P.
United Kingdom, Manchester
The University of Manchester
Ray, David
United Kingdom, Manchester
The University of Manchester
Statistics
Citations: 60
Authors: 11
Affiliations: 2
Identifiers
Doi:
10.1371/journal.pone.0015766
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics