DOI: 10.1530/JOE-16-0483 http://joe.endocrinology-journals.org © 2017 Society for Endocrinology Printed in Great Britain Published by Bioscientifica Ltd. Journal of Endocrinology 25–36 A BOELEN and others Peripheral thyroid hormones during illness Research 233:1 Tissue thyroid hormone metabolism is diferentially regulated during illness in mice Anita Boelen 1 , Anne H van der Spek 1 , Flavia Bloise 1 , Emmely M de Vries 1 , Olga V Surovtseva 1 , Mieke van Beeren 1 , Mariette T Ackermans 2 , Joan Kwakkel 1 and Eric Fliers 1 1 Department of Endocrinology & Metabolism, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 2 Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Abstract Illness induces major modifcations in central and peripheral thyroid hormone (TH) metabolism, so-called nonthyroidal illness syndrome (NTIS). As a result, organ-specifc 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-specifc 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 infammation by intraperitoneal injection of bacterial endotoxin (LPS), (2) chronic local infammation by a turpentine injection in the hind limb and (3) severe pneumonia and sepsis by intranasal inoculation with Streptococcus pneumoniae. We 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 T 3 action is differentially affected. These observations help to understand the complex nature of the nonthyroidal illness syndrome. Introduction During illness, thyroid hormone metabolism changes profoundly. Serum thyroid hormones decrease and the classical negative feedback loop of the hypothalamic– pituitary–thyroid axis is absent. This is known as the nonthyroidal illness syndrome (NTIS). The common view is that NTIS results in an overall downregulation of metabolism via low serum T 3 concentrations to save energy. However, recent studies have shown that NTIS comprises a variety of changes in transcriptional and translational activity of genes involved in local thyroid hormone metabolism ranging from inhibition to activation. These peripheral changes vary per tissue as Correspondence should be addressed to A Boelen Email a.boelen@amc.uva.nl Key Words f nonthyroidal illness f muscle f liver f thyroid hormone metabolism f infammation Journal of Endocrinology (2017) 233, 25–36 Downloaded from Bioscientifica.com at 12/17/2018 10:36:01PM via free access