title: In vivo activation of the interleukin-6 receptor/gp130 signaling pathway in pituitary corticotropes of lipopolysaccharide-treated rats.
abstract: Adrenocorticotropic hormone (ACTH) release from anterior pituitary corticotropes is greatly increased during peripheral inflammation induced by lipopolysaccharide (LPS) administration. Interleukin-6 (IL-6) is thought to participate in LPS-induced ACTH release, but whether or not corticotropes are directly targeted by this cytokine is unclear. Therefore, we investigated the expression and activation of IL-6 signaling components in the pituitary of rats 2 and 4 h after administration of LPS (250 microg/kg). Intraperitoneal LPS treatment provoked the nuclear translocation of signal transducer and activator of transcription 3 (STAT-3) and Fos expression in the anterior pituitary lobe, as demonstrated by immunohistochemistry. By using in situ hybridization, we demonstrated that suppressor of cytokine signaling 3 (SOCS-3) and c-fos mRNAs were significantly induced by the LPS treatment in the anterior lobe of the pituitary. Dual in situ hybridization revealed that most corticotropes expressed IL-6 receptor and gp130 mRNAs, and that 2 h after LPS treatment, SOCS-3 and c-fos mRNAs were induced in corticotropes. Our results suggest that LPS-induced IL-6 could regulate the hypothalamo-pituitary-adrenal axis by directly targeting corticotropes during peripheral inflammation.
authors.affiliation: Laboratoire des Régulations Neuroendocriniennes, EA 2972, Université Bordeaux I, Talence, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gautron
authors.forename: Pierrette
authors.initials: P
authors.lastname: Lafon
authors.forename: Gérard
authors.initials: G
authors.lastname: Tramu
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D017403:In Situ Hybridization; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000032:analysis; D011506:Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000378:metabolism*; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494201:Il6st protein, rat; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050822:Cytokine Receptor gp130; D011333:Pro-Opiomelanocortin