title: Thyroid hormone receptor β mediates acute illness-induced alterations in central thyroid hormone metabolism.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. a.boelen@amc.uva.nl
authors.forename: A
authors.initials: A
authors.lastname: Boelen
authors.forename: J
authors.initials: J
authors.lastname: Kwakkel
authors.forename: O
authors.initials: O
authors.lastname: Chassande
authors.forename: E
authors.initials: E
authors.lastname: Fliers
mesh_terms: 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*
chemical_list: D008070:Lipopolysaccharides; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D007453:Iodide Peroxidase