title: Sick euthyroid syndrome is associated with decreased TR expression and DNA binding in mouse liver.
abstract: Infection is associated with low serum thyroid hormones and thyrotropin levels. Here we demonstrate that infection also reduces thyroid hormone receptor (TR) expression. In gel shift experiments, retinoid X receptor (RXR)/TR DNA binding was reduced in mouse liver by 60 and 77%, respectively, 4 and 16 h after lipopolysaccharide (LPS) administration. Surprisingly, LPS did not decrease either TR-alpha or TR-beta protein levels at 4 h, but by 16 h TR-alpha(1), TR-alpha(2), and TR-beta levels were reduced by 55, 87, and 41%, respectively. We previously reported that LPS rapidly decreases RXR protein levels in liver. Therefore, we added RXR-beta to hepatic nuclear extracts prepared 4 h after LPS treatment, which restored RXR/TR DNA binding to a level comparable to that of controls. A similar experiment conducted on extracts prepared 16 h after LPS administration did not restore RXR/TR DNA binding. We propose that decreased RXR expression is limiting for RXR/TR DNA binding at 4 h, whereas the reduction in both TR and RXR levels results in further decreased binding at 16 h.
authors.affiliation: Department of Medicine, University of California San Francisco, 94121, USA. abeigneux@gladstone.ucsf.edu
authors.forename: Anne P
authors.initials: AP
authors.lastname: Beigneux
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Moser
authors.forename: Judy K
authors.initials: JK
authors.lastname: Shigenaga
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D019281:Dimerization; D004926:Escherichia coli; D005067:Euthyroid Sick Syndromes / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements; D047488:Retinoid X Receptors; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics; D037042:Thyroid Hormone Receptors beta; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; C051065:THRSP protein, human; C501477:Thrsp protein, mouse; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014157:Transcription Factors; D004247:DNA; D008291:Malate Dehydrogenase