NEW INSIGHTS INTO THE HYPOTHALAMIC-PITUITARY-THYROID AXIS
Open accessAbstract
The discovery of thyrotropin releasing hormone (TRH) in 1969 was the definitive step in decoding the hypothalamic-pituitary thyroid (HPT) axis, thereby opening up the era of neuroendocrinology, while it also revolutionized the diagnostic and therapeutic approach to patients with thyroid diseases. TRH, produced in the hypothalamus, is the central regulator of the HPT. It functions via neurons originating in the paraventricular nucleus (PVN), which integrates multiple neuronal and humoral signals and resets the HPT axis according to variations of external and internal environmental conditions. The TRH activates TSH in the pituitary that stimulates the secretion of thyroxine from thyroid which, in turn, exerts a negative feedback on TSH and TRH secretion. However, various factors are involved in the regulation of the HPT axis. Leptin has both indirect and direct effects on TRH regulation, the former by regulating agouti-related peptide (AGRP) in the arcuate nucleus (ARN) that antagonizes the α-MSH stimulatory activity on pro-TRH gene expression in the PVN, and the latter by stimulating hypothalamic TRH expression, TRH transcription via stimulation of pro-convertase 1 and 2 expression, which lead to enhanced processing of pro-TRH into TRH. The interplay of TRH with leptin and the recently reported influence of ghrelin on the HPT axis can alter the setpoint of the axis. The polyphenol resveratrol, as recently observed, exerts an anxiolytic and antidepressant activity in subclinical hypothyroid (SCH) rats. Resveratrol, by decreasing both TSH and TRH mRNA expression, regulates the HPT axis, while in parallel it regulates the Wnt/β-catenin pathway in the hippocampus. These findings open up possibilities for the therapeutic use of resveratrol as coadjuvant, especially in overt and SCH states marked by anxiety and depression. The clinician should be aware of clinical changes that can invalidate the normal regulation of the HPT axis, the most commonly observed being medications and comorbidities.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The classical feedback regulation of the HPT axis is the primary mechanism for chronically maintaining circulating free TH levels within the physiological range.
“The classical feedback regulation of the HPT axis is the primary mechanism for chronically maintaining the circulating free TH levels within the physiological range (15).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [15]
The Introduction (pp. 126–127) describes thyroid-hormone feedback on TRH and TSH and calls TRH’s role in thyroid homeostasis well established. It does not specifically establish that classical feedback is the primary mechanism for chronically keeping circulating free thyroid-hormone levels within the physiological range. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00177 · Cited by 143 · see citing works
Sánchez, E., Vargas, M. A., Singru, P. S., Pascual, I., Romero, F., Fekete, C., Charli, J.-L., & Lechan, R. M. (2009) · Endocrinology · doi:10.1210/en.2008-1643 · Cited by 110 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [2]2. Burgus R, Dunn RF, Desiderio D, Guillemin R. Stucture moleculaire du facteur hypothalamique hypophysiotrope TRF d'origine ovine: evidence par spectometrie de masse de la seequence PGA-His-Pro-NH2. CR Acad Sci (Paris) 1969 ; 269: 1870-1873.
- [3]3. Schally AV, Redding TW, Bowers CY, Barett JF. Isolation and properties of porcine thyrotropin-releasing hormone. J Biol Chem 1969; 244: 4077-4081.
- [4]4. Geoffrey Raisman. 60 years of neuroendocrinology: Memoir: Geoffrey Harris and my brush with his unit. J Endocrinology 2015; 226 (2): T1-T11.
- [5]5. Yamada M, Saga Y, Shibusawa N, Hirato J, Murakami M, Iwasaki T, Hashimoto K, Satoh T, Wakabayashi K, Taketo MM, Mori M. Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene. Proc Natl Acad Sci U S A. 1997; 94(20):10862-10867.
- [6]6. Beck-Peccoz P, Persani L, Calebiro D, Bonomi M, Mannavola D, Campi I. Syndromes of hormone resistance in the hypothalamic- pituitary-thyroid axis. Best Pract Res Clin Endocrinol Metab. 2006; 20(4):529-546. Figure 1. Light microscopic micrograph of testis in control group. New insights into the hypothalamic-pituitary-thyroid axis 129
Cited by
Sorted by citations
Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
- Authors
- Duntas, L.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Duntas, L
- ORCID
- Duntas, L
- Venue
- Acta Endocrinologica (Bucharest)
- Publisher
- ACTA Endocrinologica Foundation
- Published
- 2016
- Volume
- 12
- Issue
- 2
- Pages
- 125-129
- ISSN
- 1841-0987 (ISSN-L)
- 1843-066X
- PMC
- PMC6535279
- OpenAlex
- W2503522465
- Cited by
- 7
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2019: 1 · 2017: 1
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Endocrinologica (Bucharest) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- hypothalamic-pituitary-thyroid axis, thyrotropin-releasing hormone, paraventricular nucleus, leptin, agouti-related protein, ghrelin, resveratrol, subclinical hypothyroidism, Wnt/β-catenin signaling, anxiety, depression, thyroid dysfunction, negative feedback regulation
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 ›
Are you an author, or do you see a problem with this page? Request a review
