Thyroid hormone receptor isoform expression in livers of critically ill patients

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.

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.

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.

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.