Chronic local inflammation in mice results in decreased TRH and type 3 deiodinase mRNA expression in the hypothalamic paraventricular nucleus independently of diminished food intake
Open accessAbstract
During illness, changes in thyroid hormone metabolism occur, known as nonthyroidal illness and characterised by decreased serum triiodothyronine (T 3 ) and thyroxine (T 4 ) without an increase in TSH. A mouse model of chronic illness is local inflammation, induced by a turpentine injection in each hind limb. Although serum T 3 and T 4 are markedly decreased in this model, it is unknown whether turpentine administration affects the central part of the hypothalamus–pituitary–thyroid axis (HPT-axis). We therefore studied thyroid hormone metabolism in hypothalamus and pituitary of mice during chronic inflammation induced by turpentine injection. Using pair-fed controls, we could differentiate between the effects of chronic inflammation per se and the effects of restricted food intake as a result of illness. Chronic inflammation increased interleukin (IL)-1β mRNA expression in the hypothalamus more rapidly than in the pituitary. This hypothalamic cytokine response was associated with a rapid increase in local D2 mRNA expression. By contrast, no changes were present in pituitary D2 expression. TSHβ mRNA expression was altered compared with controls. Comparing chronic inflamed mice with pair-fed controls, both preproTSH releasing hormone (TRH) and D3 mRNA expression in the paraventricular nucleus were significantly lower 48 h after turpentine administration. The timecourse of TSHβ mRNA expression was completely different in inflamed mice compared with pair-fed mice. Turpentine administration resulted in significantly decreased TSHβ mRNA expression only after 24 h while later in time it was lower in pair-fed controls. In conclusion, central thyroid hormone metabolism is altered during chronic inflammation and this cannot solely be attributed to diminished food intake.
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Reduced hypothalamic TRH expression, portal serum TRH and pituitary TSH content have been observed both in NTIS patients and NTIS animal models.
“Indeed, reduced hypothalamic TRH expression, portal serum TRH and pituitary TSH content have been observed both in NTIS patients [65] and NTIS animal models [12, 19, 66, 67].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [19]
The Results section (page not provided) reports reduced preproTRH mRNA in the hypothalamic PVN of mice with chronic inflammation. The Discussion reports reduced pituitary TSHβ mRNA, not pituitary TSH content; the paper does not report portal-serum TRH measurements. This supports only part of the claim as applied to NTIS animal models, not the separate patient claim cited to another source. (LLM, conf=0.89)
Experimental — accuracy not yet measuredIllness 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 [19]
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Mebis, L., Langouche, L., & den Berghe, G. V. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-177-6_10 · Cited by 2 · see citing works
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Abramova, N., & Pashkovska, N. V. (2017) · Likarska sprava · doi:10.31640/ls-2017(1-2)04 · Cited by 1 · see citing works
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Miljić, D., Pekić, S., Stojanovic, M., & POPOVIC, V. M. (2018) · Endocrinology · doi:10.1007/978-3-319-44444-4_6 · Cited by 1 · see citing works
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Miljić, D., Pekić, S., Stojanovic, M., & POPOVIC, V. M. (2017) · Endocrinology · doi:10.1007/978-3-319-38681-2_6-1
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- Authors
- Boelen, A., Kwakkel, J., Wiersinga, W. M., & Fliers, E.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2006-12
- Volume
- 191
- Issue
- 3
- Pages
- 707-714
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2132313787
- Cited by
- 64
- References
- 41
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 6 · 2012: 1
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- hypothalamic-pituitary-thyroid axis, thyrotropin-releasing hormone, type 3 deiodinase, type 2 deiodinase, paraventricular nucleus, hypothalamus, pituitary gland, IL-1β, thyroid hormone metabolism, low T3 syndrome, dietary restriction, pair-fed control
- MeSH terms
- Abscess, Animals, Chronic Disease, Eating, Female, Hindlimb, Hypothalamus, Inflammation, Iodide Peroxidase, Mice, Inbred C57BL, Paraventricular Hypothalamic Nucleus, Pituitary Gland, RNA, Messenger, Thyroid Hormones, Thyrotropin-Releasing Hormone, Models, Animal, Mice
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