Thyroid hormone receptor β 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)-β is involved in these changes. In the present study, we investigated central thyroid hormone metabolism during lipopolysaccharide (LPS)-induced illness in TRβ(-/-) mice compared to wild-type (WT) mice. We administered a sublethal dose of LPS or saline to TRβ(-/-) and WT mice. TRβ(-/-) 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 TRβ(-/-) 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 TRβ(-/-) 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 TRβ(-/-), but not in WT mice. LPS decreased pituitary thyroid-stimulating hormone β mRNA expression in WT at 24 h but not in TRβ(-/-) mice. The peak in pituitary D2 expression at t = 4 h in WT was absent in TRβ(-/-) 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 TRβ(-/-) mice. Our results suggest that TRβ is involved in suppression of the central component of the hypothalamic-pituitary-thyroid axis in acute illness.
Boelen
A
A
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. a.boelen@amc.uva.nl
Kwakkel
J
J
Chassande
O
O
Fliers
E
E
D000208:Acute Disease; D000818:Animals; D005260:Female; D007031:Hypothalamus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013961:Thyroid Gland / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*
D008070:Lipopolysaccharides; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D007453:Iodide Peroxidase