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The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine

Glucocorticoids (GCs) are hormones that are released in response to stressors and exhibit many activities, including immunomodulatory and anti-inflammatory activities. They are primarily synthesized in the adrenal gland but are also produced in peripheral tissues via regeneration of adrenal 11-oxo m...

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Autores principales: Ergang, Peter, Vagnerová, Karla, Hermanová, Petra, Vodička, Martin, Jágr, Michal, Šrůtková, Dagmar, Dvořáček, Václav, Hudcovic, Tomáš, Pácha, Jiří
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073041/
https://www.ncbi.nlm.nih.gov/pubmed/33921780
http://dx.doi.org/10.3390/ijms22084229
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author Ergang, Peter
Vagnerová, Karla
Hermanová, Petra
Vodička, Martin
Jágr, Michal
Šrůtková, Dagmar
Dvořáček, Václav
Hudcovic, Tomáš
Pácha, Jiří
author_facet Ergang, Peter
Vagnerová, Karla
Hermanová, Petra
Vodička, Martin
Jágr, Michal
Šrůtková, Dagmar
Dvořáček, Václav
Hudcovic, Tomáš
Pácha, Jiří
author_sort Ergang, Peter
collection PubMed
description Glucocorticoids (GCs) are hormones that are released in response to stressors and exhibit many activities, including immunomodulatory and anti-inflammatory activities. They are primarily synthesized in the adrenal gland but are also produced in peripheral tissues via regeneration of adrenal 11-oxo metabolites or by de novo synthesis from cholesterol. The present study investigated the influence of the microbiota on de novo steroidogenesis and regeneration of corticosterone in the intestine of germ-free (GF) and specific pathogen-free mice challenged with a physical stressor (anti-CD3 antibody i.p. injection). In the small intestine, acute immune stress resulted in increased mRNA levels of the proinflammatory cytokines IL1β, IL6 and Tnfα and genes involved in de novo steroidogenesis (Stard3 and Cyp11a1), as well as in regeneration of active GCs from their 11-oxo metabolites (Hsd11b1). GF mice showed a generally reduced transcriptional response to immune stress, which was accompanied by decreased intestinal corticosterone production and reduced expression of the GC-sensitive marker Fkbp5. In contrast, the interaction between stress and the microbiota was not detected at the level of plasma corticosterone or the transcriptional response of adrenal steroidogenic enzymes. The results indicate a differential immune stress-induced intestinal response to proinflammatory stimuli and local corticosterone production driven by the gut microbiota.
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spelling pubmed-80730412021-04-27 The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine Ergang, Peter Vagnerová, Karla Hermanová, Petra Vodička, Martin Jágr, Michal Šrůtková, Dagmar Dvořáček, Václav Hudcovic, Tomáš Pácha, Jiří Int J Mol Sci Article Glucocorticoids (GCs) are hormones that are released in response to stressors and exhibit many activities, including immunomodulatory and anti-inflammatory activities. They are primarily synthesized in the adrenal gland but are also produced in peripheral tissues via regeneration of adrenal 11-oxo metabolites or by de novo synthesis from cholesterol. The present study investigated the influence of the microbiota on de novo steroidogenesis and regeneration of corticosterone in the intestine of germ-free (GF) and specific pathogen-free mice challenged with a physical stressor (anti-CD3 antibody i.p. injection). In the small intestine, acute immune stress resulted in increased mRNA levels of the proinflammatory cytokines IL1β, IL6 and Tnfα and genes involved in de novo steroidogenesis (Stard3 and Cyp11a1), as well as in regeneration of active GCs from their 11-oxo metabolites (Hsd11b1). GF mice showed a generally reduced transcriptional response to immune stress, which was accompanied by decreased intestinal corticosterone production and reduced expression of the GC-sensitive marker Fkbp5. In contrast, the interaction between stress and the microbiota was not detected at the level of plasma corticosterone or the transcriptional response of adrenal steroidogenic enzymes. The results indicate a differential immune stress-induced intestinal response to proinflammatory stimuli and local corticosterone production driven by the gut microbiota. MDPI 2021-04-19 /pmc/articles/PMC8073041/ /pubmed/33921780 http://dx.doi.org/10.3390/ijms22084229 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ergang, Peter
Vagnerová, Karla
Hermanová, Petra
Vodička, Martin
Jágr, Michal
Šrůtková, Dagmar
Dvořáček, Václav
Hudcovic, Tomáš
Pácha, Jiří
The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
title The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
title_full The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
title_fullStr The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
title_full_unstemmed The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
title_short The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
title_sort gut microbiota affects corticosterone production in the murine small intestine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073041/
https://www.ncbi.nlm.nih.gov/pubmed/33921780
http://dx.doi.org/10.3390/ijms22084229
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