title: Glucocorticoids down-regulate lipopolysaccharide-induced de novo production of neurotensin mRNA in the rat hypothalamic, paraventricular, corticotrophin-releasing hormone neurons.
abstract: OBJECTIVE
  Intraperitoneal injection of the endotoxin lipopolysaccharide (LPS) produces inflammation accompanied by activation of the immune system and the secretion of cytokines. Cytokines stimulate the hypothalamo-pituitary-adrenal (HPA) axis to release the anti-inflammatory corticosterone which controls its own production by acting on the HPA axis. Upstream in the HPA axis are neuroendocrine corticotrophin-releasing hormone (CRH) neurons located in the paraventricular nucleus (PVN), whose multipeptidergic phenotype changes during inflammation: while CRH mRNA is up-regulated in these conditions, neurotensin (NT) mRNA expression is induced de novo. The negative feedback control of glucocorticoids on CRH production is well documented; however, their action on NT production in the PVN of the hypothalamus is poorly documented. The aim of this study was to determine if glucocorticoids modulate the de novo production of NT during inflammation.
  
  
  METHODS
  Using quantitative in situ hybridization histochemistry, we examined whether the absence (adrenalectomy) or excess (corticosterone implants) of glucocorticoids modulate de novo production of NT mRNA in the PVN during inflammation induced by LPS treatment.
  
  
  RESULTS
  A relatively low dose of LPS (50 microg/kg) that is not efficient to induce NT mRNA production in the PVN becomes efficient after adrenalectomy. Moreover, corticosterone excess reduces LPS-induced production of NT mRNA in the PVN.
  
  
  CONCLUSIONS
  Glucocorticoids exert a negative control on NT mRNA production in the PVN of the hypothalamus, and this effect requires that NT mRNA production be triggered, such as during inflammation.
authors.affiliation: Laboratoire d'Homéostasie Cellulaire et Pathologies, EA3842, Faculté de Médecine de Limoges, Limoges, France. elodie.loum@unilim.fr
authors.forename: Elodie
authors.initials: E
authors.lastname: Loum-Ribot
authors.forename: Pierrette
authors.initials: P
authors.lastname: Lafon
authors.forename: Michel
authors.initials: M
authors.lastname: Chaigniau
authors.forename: Gerard
authors.initials: G
authors.lastname: Tramu
authors.forename: Marc
authors.initials: M
authors.lastname: Corio
mesh_terms: D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D017403:In Situ Hybridization; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009496:Neurotensin / Q000096:biosynthesis*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009496:Neurotensin; D000324:Adrenocorticotropic Hormone