The DOI matches its Crossref record; 26 of the 28 references it cites were found in a registry or an index.
Simultaneous changes in central and peripheral components of the hypothalamus-pituitary-thyroid axis in lipopolysaccharide-induced acute illness in mice
Open accessAbstract
During illness, major changes in thyroid hormone metabolism and regulation occur; these are collectively known as non-thyroidal illness and are characterized by decreased serum triiodothyronine (T(3)) and thyroxine (T(4)) without an increase in serum TSH. Whether alterations in the central part of the hypothalamus-pituitary-thyroid (HPT) axis precede changes in peripheral thyroid hormone metabolism instead of vice versa, or occur simultaneously, is presently unknown. We therefore studied the time-course of changes in thyroid hormone metabolism in the HPT axis of mice during acute illness induced by bacterial endotoxin (lipopolysaccharide; LPS).LPS rapidly induced interleukin-1beta mRNA expression in the hypothalamus, pituitary, thyroid and liver. This was followed by almost simultaneous changes in the pituitary (decreased expression of thyroid receptor (TR)-beta2, TSHbeta and 5'-deiodinase (D1) mRNAs), the thyroid (decreased TSH receptor mRNA) and the liver (decreased TRbeta1 and D1 mRNA). In the hypothalamus, type 2 deiodinase mRNA expression was strongly increased whereas preproTRH mRNA expression did not change after LPS. Serum T(3) and T(4) fell only after 24 h.Our results suggested almost simultaneous involvement of the whole HPT axis in the downregulation of thyroid hormone metabolism during acute illness.
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In the citing paper
“Illness results in marked downregulation of DIO1 both in humans and experimental animals [15, 20, 21].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Liver TRα and TRβ expression in rodents decrease during acute illness [15, 39] but not during chronic inflammation and bacterial sepsis.”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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 [15]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, liver TRβ1 expression decreases during acute inflammation in mice [15, 39, 77] and limited availability of SRC-1, a shared coactivator for TR and inflammatory signaling pathways, might be partly responsible for the illness induced decrease of liver DIO1 [78, 79].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Together, this suggested almost simultaneous involvement of the whole HPT axis in the downregulation of thyroid hormone metabolism during acute illness [15].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Serum T3 and T4 fell only after 24 h.”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“In the hypothalamus, D2 mRNA was strongly increased whereas preproTRH mRNA expression did not change after LPS.”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“This was followed by almost simultaneous molecular changes in the pituitary, the thyroid gland and the liver.”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Studies in mice on the time course of the changes in thyroid hormone metabolism in the HPT axis during acute illness induced by bacterial endotoxin (lipopolysaccharide; LPS) showed a rapid induction of interleukin-1beta mRNA expression in the hypothalamus, pituitary, thyroid and liver.”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Liver DIO3 is differentially regulated during illness: acute inflammation in mice results in decreased DIO3 levels [15] but prolonged critical illness, both in patients and in rabbits, increases DIO3 [21, 22].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [15]
Experimental — accuracy not yet measuredIn the citing paper
“LPS has a potent effect on tanycyte D2 gene expression and enzymatic activity, resulting in an approximately 4-fold increase of D2 mRNA level and activity in the MBH within 12 hours of administration (Figure 15, A and B) (197,200).”
From Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions (2014) · cites this paper as [200]
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Metadata
- Authors
- Boelen, A., Kwakkel, J., Thijssen-Timmer, D., Alkemade, A., Fliers, E., & Wiersinga, W.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2004-08-01
- Volume
- 182
- Issue
- 2
- Pages
- 315-323
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2106664880
- Cited by
- 159
- References
- 28
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 9 · 2013: 5 · 2012: 2
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (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
- hypothalamic-pituitary-thyroid axis, low T3 syndrome, lipopolysaccharide, acute illness, thyroid hormone metabolism, triiodothyronine, thyroxine, thyroid-stimulating hormone, type 2 deiodinase, thyroid hormone receptor beta, IL-1β, endotoxin, mice
- MeSH terms
- Acute Disease, Animals, Bacterial Infections, Female, Gene Expression Regulation, Hypothalamo-Hypophyseal System, Interleukin-1, Iodide Peroxidase, Lipopolysaccharides, Liver, Mice, Inbred BALB C, Receptors, Thyrotropin, RNA, Messenger, Thyroid Hormones, Thyroid Hormone Receptors beta, Thyrotropin, beta Subunit, Mice
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