Contribution of TNF-α and nuclear factor-κB signaling to type 2 iodothyronine deiodinase activation in the mediobasal hypothalamus after lipopolysaccharide administration

Edith Sanchez, Praful S. Singru, Gabor Wittmann, Shira S. Nouriel, Perry Barrett, Csaba Fekete, Ronald M. Lechan

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21 Citations (Scopus)

Abstract

To determine whether signaling through TNF and/or nuclear factor-κB contributes to bacterial lipopolysaccharide (LPS)-induced activation of type 2 iodothyronine deiodinase (D2) in tanycytes lining the floor and infralateral walls of the third ventricle, the effect of a TNF antagonist on D2 gene expression and LPS-induced Iκ-Bα expression in tanycytes were studied. Animals treated with soluble, rat, polyethylene glycol-conjugated TNF receptor type 1 (4 mg/kg body weight) before a single ip injection of LPS showed a significant reduction in circulating IL-6 levels but no effect on LPS-induced D2 mRNA in the majority of tanycytes with the exception of a subpopulation of α tanycytes in the wall of the third ventricle. LPS induced a rapid increase in Iκ-Bα mRNA in the pars tuberalis and a delayed response in α tanycytes but absent in all other tanycyte subsets. The LPS-induced increase in Iκ-Bα in the pars tuberalis was associated with increased TSHβ gene expression in this tissue, but cAMP response element-binding protein (CREB) phosphorylation was observed only in a subset of α tanycytes. These data suggest that TNF and nuclear factor-κB signaling are not the primary, initiating mechanisms mediating the LPS-induced D2 response in tanycytes, but may contribute in part to sustaining the LPS-induced D2 response in a subset of α tanycytes. We hypothesize that in addition to TSH, other factors derived from the pars tuberalis may contribute to LPS-induced D2 activation in tanycytes.

D2 expressed in tanycytes is highly regulated in response to bacterial LPS and may contribute to central hypothyroidism associated with infection.

Original languageEnglish
Pages (from-to)3827-3835
Number of pages9
JournalEndocrinology
Volume151
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • tumor-necrosis-factor
  • nonthyroidal illness syndrome
  • messenger-ribonucleic-acid
  • thyroid-hormone feedback
  • photoperiodic response
  • bacterial lipopopolysaccharide
  • paraventricular nucleus
  • molecular-mechanism
  • rat hypothalamus
  • median-eminence

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