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Changes in CRH and ACTH Synthesis during Experimental and Human Septic Shock

Polito, A; Sonneville, R; Guidoux, C; Barrett, L; Viltart, O; Mattot, V; Siami, S; ... Sharshar, T; + view all (2011) Changes in CRH and ACTH Synthesis during Experimental and Human Septic Shock. PLOS ONE , 6 (11) , Article e25905. 10.1371/journal.pone.0025905. Green open access

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Abstract

Context The mechanisms of septic shock-associated adrenal insufficiency remain unclear. This study aimed at investigating the synthesis of corticotropin-releasing hormone (CRH) and vasopressin (AVP) by parvocellular neurons and the antehypophyseal expression of ACTH in human septic shock and in an experimental model of sepsis. Objective To test the hypothesis that ACTH secretion is decreased secondarily to alteration of CRH or AVP synthesis, we undertook a neuropathological study of the antehypophyseal system in patients who had died from septic shock and rats with experimental faecal peritonitis. Methods Brains obtained in 9 septic shock patients were compared to 10 nonseptic patients (controls). Parvocellular expression of AVP and CRH mRNA were evaluated by in situ hybridization. Antehypophyseal expression of ACTH, vasopressin V1b and CRH R1 receptors and parvocellular expression of iNOS in the PVN were evaluated by immunohistochemistry. The same experiments were carried out in a fecal peritonitis-induced model of sepsis. Data from septic rats with (n = 6) or without (n = 10) early death were compared to sham-operated (n = 8) animals. Results In patients and rats, septic shock was associated with a decreased expression of ACTH, unchanged expression of V1B receptor, CRHR1 and AVP mRNA, and increased expression of parvocellular iNOS compared to controls. Septic shock was also characterized by an increased expression of CRH mRNA in rats but not in patients, who notably had a greater duration of septic shock. Conclusion The present study suggests that in humans and in rats, septic shock is associated with decreased ACTH synthesis that is not compensated by its two natural secretagogues, AVP and CRH. One underlying mechanism might be increased expression of iNOS in hypothalamic parvocellular neurons.

Type: Article
Title: Changes in CRH and ACTH Synthesis during Experimental and Human Septic Shock
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0025905
Publisher version: http://dx.doi.org/10.1371/journal.pone.0025905
Language: English
Additional information: © 2011 Polito et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This study was funded by a grant from the Fondation Garches and also by CORTICUS (NCT00147004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1341416
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