Action of Specific Thyroid Hormone Receptor α1 and β1 Antagonists in the Central and Peripheral Regulation of Thyroid Hormone Metabolism in the Rat

Thyroid ◽  
2012 ◽  
Vol 22 (12) ◽  
pp. 1275-1282 ◽  
Author(s):  
Hermina C. van Beeren ◽  
Joan Kwakkel ◽  
Mariëtte T. Ackermans ◽  
Wilmar M. Wiersinga ◽  
Eric Fliers ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism

scholarly journals Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

2008 ◽  
Vol 197 (1) ◽  
pp. 151-158 ◽  
Author(s):  
J Kwakkel ◽  
O Chassande ◽  
H C van Beeren ◽  
W M Wiersinga ◽  
A Boelen
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Males And Females ◽  
Induced Changes ◽  
Thyroid Hormone Receptor Β

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)β1. One might thus expect that lacking the TRβ gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T3 during illness. In this study, we used TRβ−/− mice to evaluate the role of TRβ 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 TRβ. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRβ−/− and wild-type mice and TRβ−/− 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 TRβ−/− mice and increased in response to LPS in TRβ−/− and WT mice. Other (TRβ 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.

scholarly journals Differential effects of leptin and refeeding on the fasting-induced decrease of pituitary type 2 deiodinase and thyroid hormone receptor β2 mRNA expression in mice

2006 ◽  
Vol 190 (2) ◽  
pp. 537-544 ◽  
Author(s):  
A Boelen ◽  
J Kwakkel ◽  
X G Vos ◽  
W M Wiersinga ◽  
E Fliers
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Serum Leptin ◽  
Thyroid Hormone Metabolism ◽  
Hpt Axis ◽  
As Effects

Profound changes in thyroid hormone metabolism occur in the central part of the hypothalamus–pituitary–thyroid (HPT) axis during fasting. Hypothalamic changes are partly reversed by leptin administration, which decreases during fasting. It is unknown to what extent leptin affects the HPT axis at the level of the pituitary. We, therefore, studied fasting-induced alterations in pituitary thyroid hormone metabolism, as well as effects of leptin administration on these changes. Because refeeding rapidly increased serum leptin, the same parameters were studied after fasting followed by refeeding. Fasting for 24 h decreased serum T3 and T4 and pituitary TSHβ, type 2deiodinase (D2), and thyroid hormone receptor β2 (TRβ2) mRNA expression. The decrease in D2 and TRβ2 mRNA expression was prevented when 20 μg leptin was administered twice during fasting. By contrast, the decrease in TSHβ mRNA expression was unaffected. A single dose of leptin given after 24 h fasting did not affect decreased TSHβ, D2, and TRβ2 mRNA expression, while 4 h refeeding resulted in pituitary D2 and TRβ2 mRNA expression as observed in control mice. Serum leptin, T3, and T4 after refeeding were similar compared with leptin administration. We conclude that fasting decreases pituitary TSHβ, D2, and TRβ2 mRNA expression, which (with the exception of TSHβ) can be prevented by leptin administration during fasting. Following 24 h fasting, 4 h refeeding completely restores pituitary D2 and TRβ2 mRNA expression, while a single leptin dose is ineffective. This indicates that other postingestion signals may be necessary to modulate rapidly the fasting-induced decrease in pituitary D2 and TRβ2 mRNA expression.

scholarly journals Thyroid Hormone Receptor α Modulates Lipopolysaccharide-Induced Changes in Peripheral Thyroid Hormone Metabolism

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1959-1969 ◽  
Author(s):  
Joan Kwakkel ◽  
Olivier Chassande ◽  
Hermina C. van Beeren ◽  
Eric Fliers ◽  
Wilmar M. Wiersinga ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Acute Illness ◽  
Sublethal Dose ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Serum T3 ◽  
Thyroid Hormone Receptor Α

Acute inflammation is characterized by low serum T3 and T4 levels accompanied by changes in liver type 1 deiodinase (D1), liver D3, muscle D2, and muscle D3 expression. It is unknown at present whether thyroid hormone receptor α (TRα) plays a role in altered peripheral thyroid hormone metabolism during acute illness in vivo. We induced acute illness in TRα-deficient (TRα0/0) mice by administration of a sublethal dose of LPS. Compared with wild-type, TRα0/0 mice have lower basal serum T4 and lower liver D1 activity and muscle D3 mRNA expression, whereas liver D3 activity is higher. These changes are gender specific. The inflammatory response to LPS was similar in WT and TRα0/0 mice. The decrease in serum thyroid hormones and liver D1 was attenuated in TRα0/0 mice, whereas the LPS induced fall in liver D3 mRNA was more pronounced in TRα0/0 mice. Muscle D2 mRNA increased similarly in both strains, whereas muscle D3 mRNA decreased less pronounced in TRα0/0 mice. We conclude that alterations in peripheral thyroid hormone metabolism induced by LPS administration are partly regulated via TRα.

scholarly journals Thyroid Hormone Receptor α Modulates Lipopolysaccharide-Induced Changes in Peripheral Thyroid Hormone Metabolism

2010 ◽  
Vol 95 (3) ◽  
pp. 1473-1473
Author(s):  
Joan Kwakkel ◽  
Olivier Chassande ◽  
Hermina C. van Beeren ◽  
Eric Fliers ◽  
Wilmar M. Wiersinga ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Induced Changes ◽  
Thyroid Hormone Receptor Α
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