title: Time course of the response to ACTH in pig: biological and transcriptomic study.
abstract: 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 (F D R<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.
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. valerie.sautron@toulouse.inra.fr.|Université de Toulouse INPT ENSAT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. valerie.sautron@toulouse.inra.fr.|Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Toulouse, F-31076, France. valerie.sautron@toulouse.inra.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Sautron
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. elena.terenina@toulouse.inra.fr.|Université de Toulouse INPT ENSAT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. elena.terenina@toulouse.inra.fr.|Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Toulouse, F-31076, France. elena.terenina@toulouse.inra.fr.
authors.forename: Elena
authors.initials: E
authors.lastname: Terenina
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. laure.gress@toulouse.inra.fr.|Université de Toulouse INPT ENSAT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. laure.gress@toulouse.inra.fr.|Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Toulouse, F-31076, France. laure.gress@toulouse.inra.fr.
authors.forename: Laure
authors.initials: L
authors.lastname: Gress
authors.affiliation: INRA, UMR 1331 ToxAlim, Toulouse, F-31027, France. yannick.lippi@toulouse.inra.fr.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Lippi
authors.affiliation: INRA, UE 1372 GenESI, Surgeres, F-17700, France. yvon.billon@magneraud.inra.fr.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Billon
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. catherine.larzul@toulouse.inra.fr.|Université de Toulouse INPT ENSAT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. catherine.larzul@toulouse.inra.fr.|Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Toulouse, F-31076, France. catherine.larzul@toulouse.inra.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Larzul
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. laurence.liaubet@toulouse.inra.fr.|Université de Toulouse INPT ENSAT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. laurence.liaubet@toulouse.inra.fr.|Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Toulouse, F-31076, France. laurence.liaubet@toulouse.inra.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Liaubet
authors.affiliation: INRA, UR 0875 MIAT Mathématiques et Informatique Appliquées de Toulouse, Castanet-Tolosan, F-31326, France. nathalie.villa@toulouse.inra.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Villa-Vialaneix
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. pierre.mormede@toulouse.inra.fr.|Université de Toulouse INPT ENSAT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet-Tolosan, F-31326, France. pierre.mormede@toulouse.inra.fr.|Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, Toulouse, F-31076, France. pierre.mormede@toulouse.inra.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mormède
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D008297:Male; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013552:Swine; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone