Contribution of TNF-α and Nuclear Factor-κB Signaling to Type 2 Iodothyronine Deiodinase Activation in the Mediobasal Hypothalamus after Lipopolysaccharide Administration

To determine whether signaling through TNF and/or nuclear factor-kappa B 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 I kappa-B alpha 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 alpha tanycytes in the wall of the third ventricle. LPS induced a rapid increase in I kappa-B alpha mRNA in the pars tuberalis and a delayed response in alpha tanycytes but absent in all other tanycyte subsets. The LPS-induced increase in I kappa-B alpha in the pars tuberalis was associated with increased TSH beta gene expression in this tissue, but cAMP response element-binding protein (CREB) phosphorylation was observed only in a subset of alpha tanycytes. These data suggest that TNF and nuclear factor-kappa B 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 alpha tanycytes. We hypothesize that in addition to TSH, other factors derived from the pars tuberalis may contribute to LPS-induced D2 activation in tanycytes. (Endocrinology 151: 3827-3835, 2010)