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  • Title: Thyroid hormone receptor isoform expression in livers of critically ill patients.
    Author: Thijssen-Timmer DC, Peeters RP, Wouters P, Weekers F, Visser TJ, Fliers E, Wiersinga WM, Bakker O, Van Den Berghe G.
    Journal: Thyroid; 2007 Feb; 17(2):105-12. PubMed ID: 17316111.
    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. DESIGN: 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. MAIN OUTCOME: 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. CONCLUSION: 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.
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