In vivo activation of the interleukin-6 receptor/gp130 signaling pathway in pituitary corticotropes of lipopolysaccharide-treated rats

Neuroendocrinology. 2003 Jan;77(1):32-43. doi: 10.1159/000068336.


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.

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / physiology
  • In Situ Hybridization
  • Lipopolysaccharides / pharmacology*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Pituitary Gland / cytology
  • Pituitary Gland / metabolism*
  • Pro-Opiomelanocortin / analysis
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin-6 / analysis
  • Receptors, Interleukin-6 / metabolism*
  • Repressor Proteins*
  • STAT3 Transcription Factor
  • Signal Transduction / physiology*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators / metabolism
  • Transcription Factors*
  • Up-Regulation / drug effects


  • Antigens, CD
  • DNA-Binding Proteins
  • Il6st protein, rat
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Interleukin-6
  • Repressor Proteins
  • STAT3 Transcription Factor
  • Socs3 protein, rat
  • Stat3 protein, rat
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators
  • Transcription Factors
  • Cytokine Receptor gp130
  • Pro-Opiomelanocortin