Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: To explore individual variation in the biological response to cortisol, the main stress hormone, in pigs, we have developed a microarray analysis to study the kinetics of the response to an ACTH injection measured at 4 time points. ACTH is a hormone secreted by the pituitary gland and triggering the release of cortisol by the adrenal glands in response to a stress. The objective was to identify genes up- or down-regulated during the stress response triggered by cortisol in the whole blood. To explore individual variation in the biological response to cortisol, whole blood from 30 juvenile Large White (LW) pigs was collected at 4 time point ( t = 0, +1 h, +4 h, +24 h) for a total of 120 samples. All pigs were females and were raised in two batches. Arrays were designed such that all observations of a sole individual were kept on the same array, with two individuals (one from each batch) on one array. This design secured the kinetics of the response for each individual and prevented confounding effects between batch and array. After quality and control, 120 samples were kept for normalization and analyses (represented here).

ORGANISM(S): Sus scrofa

SUBMITTER: Pierre Mormède

PROVIDER: E-GEOD-71207 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:This a model from the article: A mechanistic model of ACTH-stimulated cortisol secretion. Dempsher DP, Gann DS, Phair RD. Am J Physiol 1984 Apr;246(4 Pt 2):R587-96 6326602 , Abstract: Adrenal secretory rates of cortisol and arterial concentrations of adrenocorticotropin (ACTH) were measured in conscious trained dogs subjected to intravenous infusion of ACTH. To investigate the causal relation of ACTH to the secretion of cortisol, a mechanistic mathematical model based on current hypotheses of adrenocortical function was constructed and tested. It is widely believed that ACTH stimulates cortisol secretion through adenosine 3',5'-cyclic monophosphate (cAMP), which provides substrate cholesterol by activating cholesterol ester hydrolase and facilitating transport of cholesterol to the side-chain cleavage enzyme. In addition, cholesterol modulates its own synthesis by inhibiting beta-hydroxy-beta-methylglutaryl (HMG)-CoA reductase in the adrenocortical cell. These and other steps in the biosynthetic reaction sequence were described using differential equations subject to the additional constraints imposed by available measurements of intracellular quantities. The resulting model is consistent with many of the known characteristics of the canine adrenal response to ACTH. In this model, steady-state nonlinearities arise from cooperative binding of cAMP to its receptor protein and saturation of mitochondrial pregnenolone transport. The transient response is dominated by a depletable pool of intracellular free cholesterol. Other inferences based on the model are presented, and a quantifiable cellular basis for increased adrenal sensitivity to ACTH is proposed. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Dempsher DP, Gann DS, Phair RD. (1984) - version03 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@aukland.ac.nz The University of Auckland The Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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

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