title: Lipopolysaccharide induces type 2 iodothyronine deiodinase in the mediobasal hypothalamus: implications for the nonthyroidal illness syndrome.
abstract: To determine whether the type 2 iodothyronine deiodinase (D2), the principal central nervous system enzyme converting T(4) to biologically active T(3), is regulated in tanycytes by immune activation, D2 activity was measured in the mediobasal hypothalamus (MBH) 4, 12, and 24 h after administration of bacterial lipopolysaccharide (LPS) and compared with D2 levels in the cortex and anterior pituitary of rats. In contrast to D2 activity in the cortex and anterior pituitary that showed a steady linear increase over 24 h, which was coincident with a decline in thyroid hormone and TSH levels, D2 activity peaked in the MBH 12 h after LPS administration. By in situ hybridization, the increased D2 mRNA synthesis induced by LPS was specifically localized to tanycytes lining the third ventricle. In vitro assays in HC11 and HEK-293 cells demonstrated that the p65 subunit of nuclear factor-kappaB markedly increased both rat and human D2 genes (dio2) as analyzed by promoter assays. No activation of human dio2 was observed when an 83-bp minimal promoter was used. We propose that LPS or LPS-induced cytokines directly induce D2 mRNA in tanycytes. The ensuing MBH-specific D2-mediated local thyrotoxicosis may suppress the hypothalamus-pituitary-thyroid axis by local feedback inhibition of hypophysiotropic TRH and/or TSH and contribute to the mechanism of central hypothyroidism associated with infection.
authors.affiliation: Department of Endocrine and Behavioral Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
authors.forename: Csaba
authors.initials: C
authors.lastname: Fekete
authors.forename: Balázs
authors.initials: B
authors.lastname: Gereben
authors.forename: Márton
authors.initials: M
authors.lastname: Doleschall
authors.forename: John W
authors.initials: JW
authors.lastname: Harney
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Dora
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
authors.forename: Sumit
authors.initials: S
authors.lastname: Sarkar
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Liposits
authors.forename: William
authors.initials: W
authors.lastname: Rand
authors.forename: Charles
authors.initials: C
authors.lastname: Emerson
authors.forename: Imre
authors.initials: I
authors.lastname: Kacskovics
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lechan
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002540:Cerebral Cortex / Q000201:enzymology; D004790:Enzyme Induction; D006728:Hormones / Q000097:blood; D006801:Humans; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D051996:Transcription Factor RelA; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D006728:Hormones; D007453:Iodide Peroxidase; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000097564:Iodothyronine Deiodinase Type II