title: Tissue thyroid hormone metabolism is differentially regulated during illness in mice.
abstract: Illness induces major modifications in central and peripheral thyroid hormone (TH) metabolism, so-called nonthyroidal illness syndrome (NTIS). As a result, organ-specific changes in local TH availability occur depending on the type and severity of illness. Local TH availability is of importance for the regulation of the tissue-specific TH target genes and determined by the interplay between deiodinating enzymes, TH transport and TH receptor (TR) expression. In the present study, we evaluated changes in TH transport, deiodination and TR expression, the resulting tissue TH concentrations and the expression of TH target genes in liver and muscle in three animal models of illness. We induced (1) acute systemic inflammation by intraperitoneal injection of bacterial endotoxin (LPS), (2) chronic local inflammation by a turpentine injection in the hind limb and (3) severe pneumonia and sepsis by intranasal inoculation withStreptococcus pneumoniaeWe found that all aspects of peripheral TH metabolism are differentially regulated during illness, depending on the organ studied and severity of illness. In addition, tissue TH concentrations are not equally affected by the decrease in serum TH concentrations. For example, the decrease in muscle TH concentrations is less severe than the decrease observed in liver. In addition, despite lower TH concentrations in muscle in all three models, muscle T3action is differentially affected. These observations help to understand the complex nature of the nonthyroidal illness syndrome.
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands a.boelen@amc.uva.nl.
authors.forename: Anita
authors.initials: A
authors.lastname: Boelen
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anne H
authors.initials: AH
authors.lastname: van der Spek
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Flavia
authors.initials: F
authors.lastname: Bloise
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Emmely M
authors.initials: EM
authors.lastname: de Vries
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Surovtseva
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mieke
authors.initials: M
authors.lastname: van Beeren
authors.affiliation: Department of Clinical ChemistryLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mariette T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Joan
authors.initials: J
authors.lastname: Kwakkel
authors.affiliation: Department of Endocrinology & MetabolismLaboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007249:Inflammation / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D011014:Pneumonia / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D007453:Iodide Peroxidase
keywords: inflammation; liver; muscle; nonthyroidal illness; thyroid hormone metabolism