Fasting-Induced Changes in the Hypothalamus–Pituitary–Thyroid Axis
Abstract
Fasting induces profound changes in the hypothalamus-pituitary-thyroid (HPT) axis. The alterations observed in humans and rodents are similar in many ways, although they may be more pronounced and more acute in rodents. The molecular mechanisms underlying the resetting of HPT axis regulation in the framework of caloric deprivation are still incompletely understood. Fascinating studies in rats and mice have shown a dramatic downregulation of thyrotropin-releasing hormone (TRH) gene expression in hypophysiotropic paraventricular nucleus (PVN) neurons during fasting. Direct and indirect effects of decreased serum leptin, as well as effects of increased local triiodothyronine (T3) concentrations, in the hypothalamus during food deprivation contribute to the decreased activity of TRH neurons in the PVN. However, the relative contributions of these complex determinants remain to be defined in more detail. Pituitary thyroid-stimulating hormone (TSH) beta mRNA expression decreases during fasting, and this may be relatively independent of leptin and/or TRH, since leptin administration in this setting does not fully restore pituitary TSH expression, while it does restore TRH expression in the PVN. There may be a role for pituitary peptides, such as neuromedin B, in altered TSH gene expression during fasting. The observed decrease in serum thyroid hormone concentrations results to some extent from diminished thyroidal secretion of thyroid hormones, especially in rodents. Decreased thyroxine (T4) and T3 contribute to the downregulation of T3-responsive genes such as liver D1. The overall result of these complex HPT axis changes in various tissues during fasting is downregulation of the HPT axis, which is assumed to represent an energy-saving mechanism, instrumental in times of food shortage.
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Decreased caloric intake during severe illness is likely to contribute to the development of NTIS.
“As fasting in healthy individuals induces complex changes in the HPT axis including low serum T3 without increased TSH, decreased caloric intake during severe illness is likely to contribute to the development of NTIS [90].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [90]
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Self-citation
- Authors
- Boelen, A., Wiersinga, W. M., & Fliers, E.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2008-02
- Volume
- 18
- Issue
- 2
- Pages
- 123-129
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W1963825522
- Semantic Scholar
- c2144a35bd1416b70bb5c25eeb3eaaee5f0640b2
- Cited by
- 194
- References
- 69
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 16 · 2020: 15 · 2019: 21 · 2018: 7 · 2017: 14 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 8
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (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
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- fasting, hypothalamic-pituitary-thyroid axis, thyrotropin-releasing hormone, paraventricular nucleus, leptin, triiodothyronine, thyroid-stimulating hormone, neuromedin B, thyroid hormone secretion, energy conservation, food deprivation
- MeSH terms
- Adaptation, Physiological, Animals, Energy Metabolism, Fasting, Humans, Hypothalamo-Hypophyseal System, Hypothalamus, Pituitary Gland, Thyroid Gland, Thyroid Hormones, Feedback, Physiological, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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