Ultradian cortisol pulsatility encodes a distinct, biologically important signal.
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 develope...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3022879?pdf=render |
| _version_ | 1811287956253573120 |
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| author | Andrew McMaster Maryam Jangani Paula Sommer Namshik Han Andy Brass Stephen Beesley Weiqun Lu Andrew Berry Andrew Loudon Rachelle Donn David W Ray |
| author_facet | Andrew McMaster Maryam Jangani Paula Sommer Namshik Han Andy Brass Stephen Beesley Weiqun Lu Andrew Berry Andrew Loudon Rachelle Donn David W Ray |
| author_sort | Andrew McMaster |
| collection | DOAJ |
| 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 phosphoSer(211)). 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. |
| first_indexed | 2024-04-13T03:28:35Z |
| format | Article |
| id | doaj.art-a620630caa144b97bc2a04f1b3169409 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T03:28:35Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a620630caa144b97bc2a04f1b31694092022-12-22T03:04:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1576610.1371/journal.pone.0015766Ultradian cortisol pulsatility encodes a distinct, biologically important signal.Andrew McMasterMaryam JanganiPaula SommerNamshik HanAndy BrassStephen BeesleyWeiqun LuAndrew BerryAndrew LoudonRachelle DonnDavid W RayCONTEXT: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 phosphoSer(211)). 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.http://europepmc.org/articles/PMC3022879?pdf=render |
| spellingShingle | Andrew McMaster Maryam Jangani Paula Sommer Namshik Han Andy Brass Stephen Beesley Weiqun Lu Andrew Berry Andrew Loudon Rachelle Donn David W Ray Ultradian cortisol pulsatility encodes a distinct, biologically important signal. PLoS ONE |
| title | Ultradian cortisol pulsatility encodes a distinct, biologically important signal. |
| title_full | Ultradian cortisol pulsatility encodes a distinct, biologically important signal. |
| title_fullStr | Ultradian cortisol pulsatility encodes a distinct, biologically important signal. |
| title_full_unstemmed | Ultradian cortisol pulsatility encodes a distinct, biologically important signal. |
| title_short | Ultradian cortisol pulsatility encodes a distinct, biologically important signal. |
| title_sort | ultradian cortisol pulsatility encodes a distinct biologically important signal |
| url | http://europepmc.org/articles/PMC3022879?pdf=render |
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