PMID- 23296981 OWN - NLM STAT- MEDLINE DCOM- 20130808 LR - 20130319 IS - 1479-6813 (Electronic) IS - 0952-5041 (Linking) VI - 50 IP - 2 DP - 2013 Apr TI - Septic shock non-thyroidal illness syndrome causes hypothyroidism and conditions for reduced sensitivity to thyroid hormone. PG - 255-66 LID - 10.1530/JME-12-0188 [doi] AB - Non-thyroidal illness syndrome (NTIS) is part of the neuroendocrine response to stress, but the significance of this syndrome remains uncertain. The aim of this study was to investigate the effect of lipopolysaccharide (LPS)-induced NTIS on thyroid hormone (TH) levels and TH molecular targets, as well as the relationship between septic shock nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and TH receptor beta (THRB) gene expression at a multi-tissue level in a pig model. Prepubertal domestic pigs were given i.v. saline or LPS for 48 h. Serum and tissue TH was measured by chemiluminescence and RIA. Expression of THRs and cofactors was measured by real-time PCR, and deiodinase (DIO) activity was measured by enzyme assays. Tissue NF-kB nuclear binding activity was evaluated by EMSA. LPS-treated pigs had decreased TH levels in serum and most tissues. DIO1 expression in liver and kidney and DIO1 activity in kidney decreased after LPS. No changes in DIO2 activity were observed between groups. LPS induced an increase in hypothalamus, thyroid, and liver DIO3 activity. Among the other studied genes, monocarboxylate transporter 8 and THRB were the most commonly repressed in endotoxemic pigs. LPS-induced NF-kB activation was associated with a decrease in THRB gene expression only in frontal lobe, adrenal gland, and kidney cortex. We conclude that LPS-induced NTIS in pigs is characterized by hypothyroidism and tissue-specific reduced TH sensitivity. The role of NF-kB in regulating THRB expression during endotoxemia, if any, is restricted to a limited number of tissues. FAU - Castro, Isabel AU - Castro I AD - Division of Endocrinology, Department of Internal Medicine, Texas Tech University Health Sciences Center School of Medicine, Lubbock, Texas 79430-9410, USA. FAU - Quisenberry, Leah AU - Quisenberry L FAU - Calvo, Rosa-Maria AU - Calvo RM FAU - Obregon, Maria-Jesus AU - Obregon MJ FAU - Lado-Abeal, Joaquin AU - Lado-Abeal J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130318 PL - England TA - J Mol Endocrinol JT - Journal of molecular endocrinology JID - 8902617 RN - 0 (Lipopolysaccharides) RN - 0 (Monocarboxylic Acid Transporters) RN - 0 (NF-kappa B) RN - 0 (Receptors, Thyroid Hormone) RN - 0 (Thyroid Hormones) RN - EC 1.11.1.8 (Iodide Peroxidase) SB - IM MH - Animals MH - Enzyme Activation MH - Euthyroid Sick Syndromes/*complications/*etiology MH - Female MH - Gene Expression Regulation MH - Hypothyroidism/*etiology MH - Iodide Peroxidase/genetics/metabolism MH - Lipopolysaccharides/administration & dosage MH - Monocarboxylic Acid Transporters/genetics MH - NF-kappa B/metabolism MH - Receptors, Thyroid Hormone/genetics MH - Shock, Septic/*complications MH - Swine MH - Thyroid Hormones/blood/*metabolism EDAT- 2013/01/09 06:00 MHDA- 2013/08/09 06:00 CRDT- 2013/01/09 06:00 PHST- 2013/01/09 06:00 [entrez] PHST- 2013/01/09 06:00 [pubmed] PHST- 2013/08/09 06:00 [medline] AID - JME-12-0188 [pii] AID - 10.1530/JME-12-0188 [doi] PST - epublish SO - J Mol Endocrinol. 2013 Mar 18;50(2):255-66. doi: 10.1530/JME-12-0188. Print 2013 Apr.