Induction of Type 2 Iodothyronine Deiodinase in the Mediobasal Hypothalamus by Bacterial Lipopolysaccharide: Role of Corticosterone

Abstract

To determine whether endotoxin-induced activation of type 2 iodothyronine deiodinase (D2) in the mediobasal hypothalamus is dependent on circulating levels of corticosterone, the effect of bacterial lipopolysaccharide (LPS) on D2 gene expression was studied in adrenalectomized, corticosterone-clamped adult, male, Sprague Dawley rats. In sham-adrenalectomized animals, LPS (250 μg/100 g body weight) increased circulating levels of corticosterone and IL-6, as well as tanycyte D2 mRNA in the mediobasal hypothalamus. Adrenalectomized, corticosterone-clamped animals showed no significant rise in corticosterone after LPS, compared with saline-treated controls but increased IL-6 levels and tanycyte D2 mRNA similar to LPS-treated sham controls. To further clarify the potential role of corticosterone in the regulation of D2 gene expression by LPS, animals were administered high doses of corticosterone to attain levels similar to that observed in the LPS-treated group. No significant increase in D2 mRNA was observed in the mediobasal hypothalamus with the exception of a small subpopulation of cells in the lateral walls of the third ventricle. These data indicate that the LPS-induced increase in D2 mRNA in the mediobasal hypothalamus is largely independent of circulating corticosterone and indicate that mechanisms other than adrenal activation are involved in the regulation of most tanycyte D2-expressing cells by endotoxin.