{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:41:52Z","timestamp":1790487712809,"version":"4.1.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"31","license":[{"start":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:00:00Z","timestamp":1500249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/J008893\/1"],"award-info":[{"award-number":["MR\/J008893\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N008936\/1"],"award-info":[{"award-number":["MR\/N008936\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["WT105618MA"],"award-info":[{"award-number":["WT105618MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"RCUK | Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/N014391\/1"],"award-info":[{"award-number":["EP\/N014391\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Our ability to respond to stress depends on a remarkably dynamic process of hormone secretion. The rapid release of glucocorticoid hormones from the adrenal glands is critical to mount such an efficient response to stress, particularly during inflammation. Although many key factors involved in this process have been studied, the way in which these factors interact dynamically with one another to regulate glucocorticoid secretion has not been investigated. Here, we develop a mathematical model of the regulatory network controlling glucocorticoid synthesis and, by combining this with in vivo experiments, show how this network governs changes in adrenal responsiveness under basal unstressed physiological conditions and under exposure to inflammatory stress.<\/jats:p>","DOI":"10.1073\/pnas.1703779114","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T21:00:34Z","timestamp":1500325234000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Dynamic responses of the adrenal steroidogenic regulatory network"],"prefix":"10.1073","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6904-2247","authenticated-orcid":false,"given":"Francesca","family":"Spiga","sequence":"first","affiliation":[{"name":"Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-6036","authenticated-orcid":false,"given":"Eder","family":"Zavala","sequence":"additional","affiliation":[{"name":"Living Systems Institute, University of Exeter, Exeter EX4 4QD, United Kingdom;"},{"name":"Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Exeter, Exeter EX4 4QD, United Kingdom;"},{"name":"EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter EX4 4QD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie J.","family":"Walker","sequence":"additional","affiliation":[{"name":"Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom;"},{"name":"Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Exeter, Exeter EX4 4QD, United Kingdom;"},{"name":"EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter EX4 4QD, United Kingdom;"},{"name":"College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter EX4 4QF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zidong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Terry","sequence":"additional","affiliation":[{"name":"Living Systems Institute, University of Exeter, Exeter EX4 4QD, United Kingdom;"},{"name":"Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Exeter, Exeter EX4 4QD, United Kingdom;"},{"name":"EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter EX4 4QD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stafford L.","family":"Lightman","sequence":"additional","affiliation":[{"name":"Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom;"},{"name":"EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter EX4 4QD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,7,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(09)90025-7"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00228516"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001341"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2009.2148"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/03091900802185970"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2008.01.009"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.04.018"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000773"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R200009-JLR200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7892608"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.11.2.9880"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2007-0370"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0941"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-105-4-911"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-107-1-137"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-67-3-379"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2014.0875"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4158\/EP11061.RA"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-16-0452"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0461"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.2.8658"},{"key":"e_1_3_3_22_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1210\/me.2003-0110","article-title":"Protein kinase A potentiates adrenal 4 binding protein\/steroidogenic factor 1 transactivation by reintegrating the subcellular dynamic interactions of the nuclear receptor with its cofactors, general control nonderepressed-5\/transformation\/transcription domain-associated protein, and suppressor, dosage-sensitive sex reversal-1: A laser confocal imaging study in living KGN cells","volume":"18","author":"Fan W","year":"2004","unstructured":"W Fan, , Protein kinase A potentiates adrenal 4 binding protein\/steroidogenic factor 1 transactivation by reintegrating the subcellular dynamic interactions of the nuclear receptor with its cofactors, general control nonderepressed-5\/transformation\/transcription domain-associated protein, and suppressor, dosage-sensitive sex reversal-1: A laser confocal imaging study in living KGN cells. Mol Endocrinol 18, 127\u2013141 (2004).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(96)00152-3"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9628984"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0215"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(86)90216-0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(88)90268-9"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110530200"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.10.011"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2010.02096.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.1.215"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1279"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601527103"},{"key":"e_1_3_3_34_2","first-page":"R164","article-title":"Temporal cascade of plasma level surges in ACTH, corticosterone, and cytokines in endotoxin-challenged rats","volume":"267","author":"Givalois L","year":"1994","unstructured":"L Givalois, , Temporal cascade of plasma level surges in ACTH, corticosterone, and cytokines in endotoxin-challenged rats. Am J Physiol 267, R164\u2013R170 (1994).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2061357"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0364OC"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2015.09.018"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-1209"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00003"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(01)00619-0"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.07.018"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0445"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/36899"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4530(02)00035-5"},{"key":"e_1_3_3_45_2","first-page":"1245","article-title":"Adrenocorticotropin increases interleukin-6 release from rat adrenal zona glomerulosa cells","volume":"130","author":"Judd AM","year":"1992","unstructured":"AM Judd, RM MacLeod, Adrenocorticotropin increases interleukin-6 release from rat adrenal zona glomerulosa cells. Endocrinology 130, 1245\u20131254 (1992).","journal-title":"Endocrinology"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/gcen.2000.7458"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.domaniend.2015.10.003"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-015-0835-8"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00224-7"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00042.2003"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2007.01605.x"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.11.010"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1137\/1.9780898718195"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1703779114","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1703779114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T02:02:56Z","timestamp":1649815376000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1703779114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,17]]},"references-count":53,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1073\/pnas.1703779114"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1703779114","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,17]]},"assertion":[{"value":"2017-07-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}