Lacking thyroid hormone receptor beta gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

The downregulation of liver deiodinase type 1 (D1) is supposed to be one of the mechanisms behind the decrease in serum tri-iodothyronine (T-3) observed during non-thyroidal illness (NTI). Liver D1 mRNA expression is positively regulated by T-3, mainly via the thyroid hormone receptor (TR)beta 1. One might thus expect that lacking the TRP gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T-3 during illness. In this study, we used TR beta(-/-) mice to evaluate the role of TR beta in lipopolysaccharide (LPS, a bacterial endotoxin)induced changes in thyroid hormone metabolism. Our results show that the LPS-induced serum T-3 and thyroxine and liver D1 decrease takes place despite the absence of TR beta. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRP-/- and wild-type mice and TRP-/- males and females, which did not result in differences in serum T-3. Serum T-3 decreased rapidly after LPS administration, followed by decreased liver D1, indicating that the contribution of liver D I during NTI may be limited with respect to decreased serum T-3 levels. Muscle D2 mRNA did not compensate for the low basal liver D1 observed in TRO-/- mice and increased in response to LPS in TR beta(-/-) and WT mice. Other (TRP independent) mechanisms like decreased thyroidal secretion and decreased binding to thyroid hormone-binding proteins probably play a role in the early decrease in serum T-3 observed in this study