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Time course of the response to ACTH in pig: biological and transcriptomic study

BACKGROUND: HPA axis plays a major role in physiological homeostasis. It is also involved in stress and adaptive response to the environment. In farm animals in general and specifically in pigs, breeding strategies have highly favored production traits such as lean growth rate, feed efficiency and p...

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Autores principales: Sautron, Valérie, Terenina, Elena, Gress, Laure, Lippi, Yannick, Billon, Yvon, Larzul, Catherine, Liaubet, Laurence, Villa-Vialaneix, Nathalie, Mormède, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650497/
https://www.ncbi.nlm.nih.gov/pubmed/26578410
http://dx.doi.org/10.1186/s12864-015-2118-8
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author Sautron, Valérie
Terenina, Elena
Gress, Laure
Lippi, Yannick
Billon, Yvon
Larzul, Catherine
Liaubet, Laurence
Villa-Vialaneix, Nathalie
Mormède, Pierre
author_facet Sautron, Valérie
Terenina, Elena
Gress, Laure
Lippi, Yannick
Billon, Yvon
Larzul, Catherine
Liaubet, Laurence
Villa-Vialaneix, Nathalie
Mormède, Pierre
author_sort Sautron, Valérie
collection PubMed
description BACKGROUND: HPA axis plays a major role in physiological homeostasis. It is also involved in stress and adaptive response to the environment. In farm animals in general and specifically in pigs, breeding strategies have highly favored production traits such as lean growth rate, feed efficiency and prolificacy at the cost of robustness. On the hypothesis that the HPA axis could contribute to the trade-off between robustness and production traits, we have designed this experiment to explore individual variation in the biological response to the main stress hormone, cortisol, in pigs. We used ACTH injections to trigger production of cortisol in 120 juvenile Large White (LW) pigs from 28 litters and the kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data. RESULTS: Cortisol level reached its peak 1 h after ACTH injection. White blood cell composition was modified with a decrease of lymphocytes and monocytes and an increase of granulocytes (FDR<0.05). Basal level of cortisol was correlated with birth and weaning weights. Microarray analysis identified 65 unique genes of which expression responded to the injection of ACTH (adjusted P<0.05). These genes were classified into 4 clusters with distinctive kinetics in response to ACTH injection. The first cluster identified genes strongly correlated to cortisol and previously reported as being regulated by glucocorticoids. In particular, DDIT4, DUSP1, FKBP5, IL7R, NFKBIA, PER1, RGS2 and RHOB were shown to be connected to each other by the glucocorticoid receptor NR3C1. Most of the differentially expressed genes that encode transcription factors have not been described yet as being important in transcription networks involved in stress response. Their co-expression may mean co-regulation and they could thus provide new patterns of biomarkers of the individual sensitivity to cortisol. CONCLUSIONS: We identified 65 genes as biological markers of HPA axis activation at the gene expression level. These genes might be candidates for a better understanding of the molecular mechanisms of the stress response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2118-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-46504972015-11-19 Time course of the response to ACTH in pig: biological and transcriptomic study Sautron, Valérie Terenina, Elena Gress, Laure Lippi, Yannick Billon, Yvon Larzul, Catherine Liaubet, Laurence Villa-Vialaneix, Nathalie Mormède, Pierre BMC Genomics Research Article BACKGROUND: HPA axis plays a major role in physiological homeostasis. It is also involved in stress and adaptive response to the environment. In farm animals in general and specifically in pigs, breeding strategies have highly favored production traits such as lean growth rate, feed efficiency and prolificacy at the cost of robustness. On the hypothesis that the HPA axis could contribute to the trade-off between robustness and production traits, we have designed this experiment to explore individual variation in the biological response to the main stress hormone, cortisol, in pigs. We used ACTH injections to trigger production of cortisol in 120 juvenile Large White (LW) pigs from 28 litters and the kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data. RESULTS: Cortisol level reached its peak 1 h after ACTH injection. White blood cell composition was modified with a decrease of lymphocytes and monocytes and an increase of granulocytes (FDR<0.05). Basal level of cortisol was correlated with birth and weaning weights. Microarray analysis identified 65 unique genes of which expression responded to the injection of ACTH (adjusted P<0.05). These genes were classified into 4 clusters with distinctive kinetics in response to ACTH injection. The first cluster identified genes strongly correlated to cortisol and previously reported as being regulated by glucocorticoids. In particular, DDIT4, DUSP1, FKBP5, IL7R, NFKBIA, PER1, RGS2 and RHOB were shown to be connected to each other by the glucocorticoid receptor NR3C1. Most of the differentially expressed genes that encode transcription factors have not been described yet as being important in transcription networks involved in stress response. Their co-expression may mean co-regulation and they could thus provide new patterns of biomarkers of the individual sensitivity to cortisol. CONCLUSIONS: We identified 65 genes as biological markers of HPA axis activation at the gene expression level. These genes might be candidates for a better understanding of the molecular mechanisms of the stress response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2118-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-17 /pmc/articles/PMC4650497/ /pubmed/26578410 http://dx.doi.org/10.1186/s12864-015-2118-8 Text en © Sautron et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sautron, Valérie
Terenina, Elena
Gress, Laure
Lippi, Yannick
Billon, Yvon
Larzul, Catherine
Liaubet, Laurence
Villa-Vialaneix, Nathalie
Mormède, Pierre
Time course of the response to ACTH in pig: biological and transcriptomic study
title Time course of the response to ACTH in pig: biological and transcriptomic study
title_full Time course of the response to ACTH in pig: biological and transcriptomic study
title_fullStr Time course of the response to ACTH in pig: biological and transcriptomic study
title_full_unstemmed Time course of the response to ACTH in pig: biological and transcriptomic study
title_short Time course of the response to ACTH in pig: biological and transcriptomic study
title_sort time course of the response to acth in pig: biological and transcriptomic study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650497/
https://www.ncbi.nlm.nih.gov/pubmed/26578410
http://dx.doi.org/10.1186/s12864-015-2118-8
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