title: Changes in CRH and ACTH synthesis during experimental and human septic shock.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Intensive Care, Raymond Poincaré Hospital, Garches, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Polito
authors.forename: Romain
authors.initials: R
authors.lastname: Sonneville
authors.forename: Céline
authors.initials: C
authors.lastname: Guidoux
authors.forename: Lucinda
authors.initials: L
authors.lastname: Barrett
authors.forename: Odile
authors.initials: O
authors.lastname: Viltart
authors.forename: Virginie
authors.initials: V
authors.lastname: Mattot
authors.forename: Shidasp
authors.initials: S
authors.lastname: Siami
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Lorin de la Grandmaison
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
authors.forename: Françoise
authors.initials: F
authors.lastname: Gray
authors.forename: Djillali
authors.initials: D
authors.lastname: Annane
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Brouland
authors.forename: Tarek
authors.initials: T
authors.lastname: Sharshar
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D052247:Nitric Oxide Synthase Type II
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