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.
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Authors | A Boelen, J Kwakkel, O Chassande, E Fliers |
Journal | Journal of neuroendocrinology
(J Neuroendocrinol)
Vol. 21
Issue 5
Pg. 465-72
(May 2009)
ISSN: 1365-2826 [Electronic] United States |
PMID | 19302190
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lipopolysaccharides
- Thyroid Hormone Receptors beta
- Thyroid Hormones
- Iodide Peroxidase
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Topics |
- Acute Disease
- Animals
- Female
- Hypothalamus
(anatomy & histology, drug effects, metabolism)
- Iodide Peroxidase
(genetics, metabolism)
- Lipopolysaccharides
(pharmacology)
- Male
- Mice
- Mice, Knockout
- Thyroid Gland
(metabolism)
- Thyroid Hormone Receptors beta
(genetics, metabolism)
- Thyroid Hormones
(metabolism)
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