Thyroid Hormone Receptor beta Mediates Acute Illness-Induced Alterations in Central Thyroid Hormone Metabolism

Acute illness in mice profoundly affects thyroid hormone metabolism in the hypothalamus and pituitary gland. It remains unknown whether the thyroid hormone receptor (TR)-beta is involved in these changes. In the present study, we investigated central thyroid hormone metabolism during lipopolysaccharide (LPS)-induced illness in TR beta(-/-) mice compared to wild-type (WT) mice. We administered a sublethal dose of LPS or saline to TR beta(-/-) and WT mice. TR beta(-/-) mice displayed higher basal levels of serum triiodothyronine (T-3) and thyroxine (T-4) compared to WT, reflecting thyroid hormone resistance. In the periventricular area of the hypothalamus, we observed a marked decrease in thyrotrophin-releasing hormone (TRH) mRNA expression in TR beta(-/-) and WT mice at t = 4 h, coinciding with the peak in plasma corticosterone. The decrease in TRH mRNA persisted in WT, but not in TR beta(-/-) mice at t = 24 h. By contrast, the increase of type 2 deiodinase (D2) mRNA already present at 4 h after LPS remained significant at 24 h in TR beta(-/-), but not in WT mice. LPS decreased pituitary thyroid-stimulating hormone beta mRNA expression in WT at 24 h but not in TR beta(-/-) mice. The peak in pituitary D2 expression at t = 4 h in WT was absent in TR beta(-/-) mice. The relative decrease in plasma T-3 and T-4 upon LPS treatment was similar in both strains, although, at t = 24 h, plasma T-3 tended to be restored in TR beta(-/-) mice. Our results suggest that TR beta is involved in suppression of the central component of the hypothalamic-pituitary-thyroid axis in acute illness