ArticleEndocrinology2023
Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism.
Article in Endocrinology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- The impact of subclinical hypothyroidism on core reproductive hormones and ovarian endocrine status in patients with polycystic ovary syndrome: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Treatment Preferences in Patients With Hypothyroidism.The Journal of clinical endocrinology and metabolism · 2025Pooled it
- A feasibility double-blind trial of levothyroxine vs. levothyroxine-liothyronine in postsurgical hypothyroidism.Frontiers in endocrinology · 2025Trial
- Review
- Signal Amplification in the HPT Axis-Evidence for Its Existence, Location, Significance, and Molecular Mechanisms.Acta physiologica (Oxford, England) · 2026Review
- Third-trimester estradiol is associated with isolated maternal hypothyroxinemia and attenuated TSH-FT4 coupling: evidence from rats and human astrocytes.Frontiers in endocrinology · 2026Article
- FVB But Not B6 Mice Carrying the Thr92Ala-Dio2 Polymorphism Have Impaired Thyroid Hormonogenesis and Goiter.Endocrinology · 2025Article
- Variable transduction of thyroid hormone signaling in structures of the mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Clinical thyroidology: beyond the 1970s' TSH-T4 Paradigm.Frontiers in endocrinology · 2025Review
- High TSH levels during TSH suppression therapy in DTC postoperative patients are associated with low DIO2 expression in the thyroid and impaired thyroid hormone sensitivity.Frontiers in endocrinology · 2025Article
- Gender-Specific DNA Methylation Profiles Associated with Adult Weight in Hezuo Pigs.International journal of molecular sciences · 2024Article
- Thyroid Hormone Homeostasis in Levothyroxine-treated Patients: Findings From ELSA-Brasil.The Journal of clinical endocrinology and metabolism · 2024Article
- Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism.Endocrinology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
The regulation of thyroid activity and thyroid hormone (TH) secretion is based on feedback mechanisms that involve the anterior pituitary TSH and medial basal hypothalamus TSH-releasing hormone. Plasma T3 levels can be "sensed" directly by the anterior pituitary and medial basal hypothalamus; plasma T4 levels require local conversion of T4 to T3, which is mediated by the type 2 deiodinase (D2). To study D2-mediated T4 to T3 conversion and T3 production in the anterior pituitary gland, we used mouse pituitary explants incubated with 125I-T4 for 48 hours to measure T3 production at different concentrations of free T4. The results were compared with cultures of D1- or D2-expressing cells, as well as freshly isolated mouse tissue. These studies revealed a unique regulation of the D2 pathway in the anterior pituitary gland, distinct from that observed in nonpituitary tissues. In the anterior pituitary, increasing T4 levels reduced D2 activity slightly but caused a direct increase in T3 production. However, the same changes in T4 levels decreased T3 production in human HSkM cells and murine C2C12 cells (both skeletal muscle) and mouse bone marrow tissue, which reached zero at 50 pM free T4. In contrast, the increase in T4 levels caused the pig kidney LLC-PK1 cells and kidney fragments to proportionally increase T3 production. These findings have important implications for both physiology and clinical practice because they clarify the mechanism by which fluctuations in plasma T4 levels are transduced in the anterior pituitary gland to mediate the TSH feedback mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.