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 (T3) observed during non-thyroidal illness (NTI). Liver D1 mRNA expression is positively regulated by T3, mainly via the thyroid hormone receptor (TR)beta1. One might thus expect that lacking the TRbeta gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T3 during illness. In this study, we used TRbeta-/- mice to evaluate the role of TRbeta in lipopolysaccharide (LPS, a bacterial endotoxin)-induced changes in thyroid hormone metabolism. Our results show that the LPS-induced serum T3 and thyroxine and liver D1 decrease takes place despite the absence of TRbeta. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRbeta-/- and wild-type mice and TRbeta-/- males and females, which did not result in differences in serum T3. Serum T3 decreased rapidly after LPS administration, followed by decreased liver D1, indicating that the contribution of liver D1 during NTI may be limited with respect to decreased serum T3 levels. Muscle D2 mRNA did not compensate for the low basal liver D1 observed in TRbeta-/- mice and increased in response to LPS in TRbeta-/- and WT mice. Other (TRbeta independent) mechanisms like decreased thyroidal secretion and decreased binding to thyroid hormone-binding proteins probably play a role in the early decrease in serum T3 observed in this study.
Kwakkel
J
J
Department of Endocrinology and Metabolism, Academic Medical Center University of Amsterdam, F5-165, Meibergdreef 9, 1105 AZ Amsterdam The Netherlands.
Chassande
O
O
van Beeren
H C
HC
Wiersinga
W M
WM
Boelen
A
A
D000208:Acute Disease; D000818:Animals; D005260:Female; D053583:Interleukin-1beta / Q000235:genetics; D007453:Iodide Peroxidase / Q000032:analysis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000502:physiology*; D013963:Thyroid Hormones / Q000378:metabolism*; D000097564:Iodothyronine Deiodinase Type II
D053583:Interleukin-1beta; D007453:Iodide Peroxidase; D008070:Lipopolysaccharides; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I