ArticleeLife2023
Axonal T3 uptake and transport can trigger thyroid hormone signaling in the brain.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Treatment Preferences in Patients With Hypothyroidism.The Journal of clinical endocrinology and metabolism · 2025Pooled it
- Multiscale characterization and distribution of the thyroid hormone transporter MCT8 in the adult and aged human brain.Acta neuropathologica communications · 2026Article
- Signal Amplification in the HPT Axis-Evidence for Its Existence, Location, Significance, and Molecular Mechanisms.Acta physiologica (Oxford, England) · 2026Review
- GluN2A-mediated currents and calcium signal in human iPSC-derived neurons.Scientific reports · 2026Article
- Cellular expression domains of type 3 deiodinase in the meninges, choroid plexus, tanycytes and barrier tissues of the brain.Frontiers in endocrinology · 2026Article
- Neurological consequences of adult-onset hypothyroidism.Endocrine journal · 2025Review
- Thyroid hormone promotes fetal neurogenesis.JCI insight · 2025Article
- Trisomy 21 Disrupts Thyroid Hormones Signaling During Human iPSC-Derived Neural Differentiation In Vitro.Cells · 2025Article
- FT3 and FT3/FT4 ratio are decreased and not compensated by levothyroxine treatment in TKI-treated thyroid cancer patients.Endocrine-related cancer · 2025Article
- Serotonergic and Chemosensory Brain Areas and Sensory Ganglia Expressing Type 3 Deiodinase Mapped With Dio3Cre drivers.Endocrinology · 2025Article
- Article
- 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
- Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice.European thyroid journal · 2025Article
- Mapping Thyroid Hormone Action in the Human Brain.Thyroid : official journal of the American Thyroid Association · 2024Review
- Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism.Endocrine · 2024Review
- Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome.JCI insight · 2024Article
- The Thr92Ala polymorphism in the type 2 deiodinase gene is linked to depression in patients with COVID-19 after hospital discharge.Frontiers in endocrinology · 2024Article
- Nongenomic roles of thyroid hormones and their derivatives in adult brain: are these compounds putative neurotransmitters?Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
The development of the brain, as well as mood and cognitive functions, are affected by thyroid hormone (TH) signaling. Neurons are the critical cellular target for TH action, with T3 regulating the expression of important neuronal gene sets. However, the steps involved in T3 signaling remain poorly known given that neurons express high levels of type 3 deiodinase (D3), which inactivates both T4 and T3. To investigate this mechanism, we used a compartmentalized microfluid device and identified a novel neuronal pathway of T3 transport and action that involves axonal T3 uptake into clathrin-dependent, endosomal/non-degradative lysosomes (NDLs). NDLs-containing T3 are retrogradely transported via microtubules, delivering T3 to the cell nucleus, and doubling the expression of a T3-responsive reporter gene. The NDLs also contain the monocarboxylate transporter 8 (Mct8) and D3, which transport and inactivate T3, respectively. Notwithstanding, T3 gets away from degradation because D3's active center is in the cytosol. Moreover, we used a unique mouse system to show that T3 implanted in specific brain areas can trigger selective signaling in distant locations, as far as the contralateral hemisphere. These findings provide a pathway for L-T3 to reach neurons and resolve the paradox of T3 signaling in the brain amid high D3 activity.
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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.