title: Thyroid hormone receptor isoform expression in livers of critically ill patients.
abstract: OBJECTIVE
  The THRA gene encodes two isoforms of the thyroid hormone receptor (TR), TRalpha1 and TRalpha2. The ratio of these splice variants could have a marked influence on T3-regulated gene expression, especially during illness.
  
  
  METHODS
  We studied the expression of the isoforms TRbeta1, TRalpha1, and TRalpha2 and 5'-deiodinase in postmortem liver biopsies of 58 patients who were critically ill and died in the intensive care unit (ICU). All mRNA levels were determined using real-time PCR.
  
  
  RESULTS
  All ratios of the biopsies were higher than those found in three normal liver biopsies due to an increased TRalpha1 level. The TRalpha1/TRalpha2 ratio increased with age and severity of illness following the equation: TRalpha1/TRalpha2 ratio = - 1.854 + (0.0323 x age) + (0.0431 x Therapeutic Intervention Scoring System score) indicating that 28% of the changed TRalpha1/TRalpha2 ratio can be predicted by these clinical variables. There was no effect of randomization to intensive insulin therapy or glucocorticoid or thyroid hormone treatment on the TRalpha1/TRalpha2 ratio or TRbeta1. Furthermore, no relation was seen between the expression levels of the 5'-deiodinase mRNA and TR isoforms or the triiodothyronine T3 levels.
  
  
  CONCLUSIONS
  It appears that in critically ill patients the ratio of TRalpha1/TRalpha2 expression increases with age and severity of illness, possibly indicating a mechanism to enhance sensitivity to T3 in the oldest and sickest patients.
authors.affiliation: Department of Endocrinology and Metabolism, F5-171, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Daphne C
authors.initials: DC
authors.lastname: Thijssen-Timmer
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.forename: Pieter
authors.initials: P
authors.lastname: Wouters
authors.forename: Frank
authors.initials: F
authors.lastname: Weekers
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: Onno
authors.initials: O
authors.lastname: Bakker
authors.forename: Greet
authors.initials: G
authors.lastname: Van Den Berghe
mesh_terms: D000368:Aged; D016638:Critical Illness; D006801:Humans; D007453:Iodide Peroxidase / Q000097:blood / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D037021:Thyroid Hormone Receptors alpha / Q000032:analysis / Q000235:genetics*; D037042:Thyroid Hormone Receptors beta / Q000032:analysis / Q000235:genetics*; D014284:Triiodothyronine / Q000097:blood
chemical_list: D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D007453:Iodide Peroxidase