Brain sampling was performed in eight sham, ten septic and six septic shock rats. Whole brains and pituitary glands were removed MDV3100 immediately after animal sacrifice by neck dislocation, and fixed by immersion in 10% formalin. Brain samples were processed as previously described. Briefly, after embedding in paraffin, serial sections of 4 mm were performed until the region of interest was reached. Coronal sections of the PVN nuclei and horizontal sections of the pituitary gland were then stained with haematoxylin and eosin before microscopic examination or treated for immunohistochemistry or in situ hybridization. This study assessed sepsis-induced ACTH expression and expression of its main regulators, both in patients and in rats. Decreased ACTH and unchanged expression of AVP mRNA, CRHR1, and V1b receptors was a consistent finding in human and in rats. Conversely, CRH mRNA expression was increased in rats with septic shock but not in patients with septic shock. These results suggest that septic shock is associated with central impairment of the HPA, characterized by decreased ACTH synthesis while its two main regulators CRH and AVP remain roughly unchanged. However, if the stimulus is repeated, plasma glucocorticoid levels are usually above basal values but plasma ACTH responses vary, being preserved or desensitized according to the nature of the stimulus. Similarly to our study, in a cecal ligation and puncture model, Carlson and colleagues showed an increase of CRH expression in PVN and a reduced adrenocortical sensitivity to ACTH during acute and post-acute phase as well as Oliveira-Pelegrin and colleagues showed no change in the paraventricular AVP expression between CLP and sham rats. It has been shown that LPS down-regulates the mRNA coding for AVP and CRH antehypophyseal receptors; however,the effect of prolonged experimental sepsis on these receptors has not been assessed yet. Given that these conclusions are comparable with our findings, we think that the originality of our work lies on a broad description of the HPA both in human and animals, in post-acute and ultimate phase of septic shock. Additionally, one may argue that variation of variable value is low. This is due to the large interval of the scores that we used, which enabled to detect clear and obvious rather than subtle and disputable difference. It reflects also the reproducibility between evaluators and the standardization of brain sampling and experimental models. Our results show that HPA axis appeared non-reactive. It seems unlikely that sepsis induced by the surgical model was not enough severe to activate HPA axis. Faecal peritonitis constitutes a sustained stimulus sufficient to induce tissue inflammation and impairment of visceral sensory pathways. It has been previously showed that CLP reflects the clinical course of sepsis and all our septic animals showed features of severe illness. Moreover, this surgical model has been used to assess central neuroendocrine response, which is likely to be present in septic patients. Our study provides just a snapshot of the HPA axis’s state at a given time of course of sepsis.