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.
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Illness results in increased hypothalamic DIO2 mRNA expression and activity while hypothalamic DIO3 decreases.
“Illness results in increased DIO2 mRNA expression and activity [12, 15–17] while hypothalamic DIO3 decreases [18, 19].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [18]
Hypothalamic TR mRNA expression does not change dramatically during NTIS, but the increase in hypothalamic DIO2 and decrease in hypothalamic DIO3 observed during acute inflammation is exaggerated in mice lacking TRβ.
“Hypothalamic TR mRNA expression does not change dramatically during NTIS [12], but the increase in hypothalamic DIO2 and decrease in hypothalamic DIO3 observed during acute inflammation is exaggerated in mice lacking TRβ [18].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [18]
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Self-citation
- Authors
- Boelen, A., Kwakkel, J., Chassande, O., & Fliers, E.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Inserm (FR)
- ORCID
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2009-04-08
- Volume
- 21
- Issue
- 5
- Pages
- 465-472
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W2092628191
- Cited by
- 32
- References
- 38
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 2
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- thyroid hormone receptor beta, acute illness, lipopolysaccharide, hypothalamic-pituitary-thyroid axis, thyrotropin-releasing hormone, type 2 deiodinase, thyroid-stimulating hormone, thyroid hormone resistance, triiodothyronine, thyroxine, corticosterone
- MeSH terms
- Acute Disease, Animals, Female, Hypothalamus, Iodide Peroxidase, Lipopolysaccharides, Male, Thyroid Gland, Thyroid Hormones, Mice, Knockout, Thyroid Hormone Receptors beta, Mice
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