Thyroid hormone receptor beta

cross_nutrient

Vitamin A-iodine: shared receptor machinery for an iodine-containing hormone; not evidence of iodine repletion.

evidence_locator

Figure 3

experimental_model

Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters.

exposure

Reconstituted TR beta/RXRA

limitations

No iodine nutritional manipulation.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors

plain_language

A receptor used by retinoids also supports thyroid-hormone DNA recognition.

primary_references

[va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

tissue_or_cell_type

Cell-free DNA-binding assay

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1109–1121

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. · source_derived_draft · unverified_draft

### va-sig-rxra-thrb-partnership RXRA complexed with TR beta and enhanced thyroid-response-element binding. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor used by retinoids also supports thyroid-hormone DNA recognition. organism: Recombinant receptors tissue_or_cell_type: Cell-free DNA-binding assay experimental_model: Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. limitations: No iodine nutritional manipulation. evidence_locator: Figure 3 cross_nutrient: Vitamin A-iodine: shared receptor machinery for an iodine-containing hormone; not evidence of iodine repletion. exposure: Reconstituted TR beta/RXRA [va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

cross_nutrient

An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation.

evidence_locator

Figure 2a and Results: structural characterization; Methods: protein production and crystallography

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 2a and Results: structural characterization; Methods: protein production and crystallography", "start_char": 10702, "end_char": 12152}]

experimental_model

Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays

exposure

Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution.

limitations

Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold.

nutrient_topic

Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine

organism

Human receptor domains produced in Escherichia coli; synthetic coactivator peptide

plain_language

T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator.

primary_references

[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

tissue_or_cell_type

Purified receptor-domain complex

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1172–1185

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays · source_derived_draft · unverified_draft

### i-met-t3-thrb-ligand-binding T3 was bound within the human THRB ligand-binding domain in the crystallized THRB–RXRA domain heterodimer, with the THRB activation surface accommodating an SRC-2-derived peptide. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator. organism: Human receptor domains produced in Escherichia coli; synthetic coactivator peptide tissue_or_cell_type: Purified receptor-domain complex experimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays limitations: Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold. exposure: Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution. cross_nutrient: An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation. evidence_locator: Figure 2a and Results: structural characterization; Methods: protein production and crystallography evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 2a and Results: structural characterization; Methods: protein production and crystallography", "start_char": 10702, "end_char": 12152}] [i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

cross_nutrient

Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence.

evidence_locator

Figure 1b and legend; Methods: Cell-based assays

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 1b and legend; Methods: Cell-based assays", "start_char": 45264, "end_char": 46014}]

experimental_model

Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays

exposure

1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments.

limitations

Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal.

nutrient_topic

Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine

organism

Full-length human receptors expressed in African green monkey CV-1 cells

plain_language

Binding of the hormone can be translated into a gene-regulatory signal through its receptor.

primary_references

[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

tissue_or_cell_type

CV-1 reporter assay

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1187–1200

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays · source_derived_draft · unverified_draft

### i-met-t3-thrb-transcription T3 increased thyroid-response-element luciferase activity in CV-1 cells transfected with full-length human THRB and RXRA. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding of the hormone can be translated into a gene-regulatory signal through its receptor. organism: Full-length human receptors expressed in African green monkey CV-1 cells tissue_or_cell_type: CV-1 reporter assay experimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays limitations: Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal. exposure: 1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments. cross_nutrient: Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence. evidence_locator: Figure 1b and legend; Methods: Cell-based assays evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 1b and legend; Methods: Cell-based assays", "start_char": 45264, "end_char": 46014}] [i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

evidence_span

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experimental_model

Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue

exposure

Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection

limitations

The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse

plain_language

Two receptors need different amounts of hormone, and only local production reaches the hungrier one.

primary_references

[cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803

tissue_or_cell_type

Brown adipose tissue

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 416–427

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue · source_derived_draft · unverified_draft

### cold-dio2-thyroid-sympathetic-synergy The authors propose that intracellularly generated T3 is required to saturate thyroid hormone receptor alpha, which has an approximately fourfold lower T3-binding affinity than receptor beta, making the deiodinase an essential component of the thyroid-sympathetic synergism required for thermal homeostasis. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Two receptors need different amounts of hormone, and only local production reaches the hungrier one. organism: Mouse tissue_or_cell_type: Brown adipose tissue experimental_model: Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue limitations: The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone. exposure: Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection evidence_span: {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"} [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803

evidence_span

{"source_cache": "artifacts/cold-research/9529258.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf", "start_char": 0, "end_char": 842, "text_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf"}

experimental_model

Cloning of PGC-1 from a brown fat cDNA library with ectopic expression in white adipose cells

exposure

Cold exposure of mice; ectopic PGC-1 expression

limitations

The founding description of the coactivator. Ectopic expression shows sufficiency in white fat cells; it does not establish the size of the contribution in vivo.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse

plain_language

Cold turns on a coactivator that switches the heat gene on through two different receptors.

primary_references

[cold-p9529258] A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. (1998). https://pubmed.ncbi.nlm.nih.gov/9529258/ DOI: 10.1016/s0092-8674(00)81410-5

tissue_or_cell_type

Brown fat and skeletal muscle

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 338–349

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning of PGC-1 from a brown fat cDNA library with ectopic expression in white adipose cells · source_derived_draft · unverified_draft

### cold-pgc1a-cold-induction PGC-1 mRNA expression is dramatically elevated on cold exposure in both brown fat and skeletal muscle, and PGC-1 greatly increases the transcriptional activity of PPARgamma and the thyroid hormone receptor on the UCP1 promoter. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Cold turns on a coactivator that switches the heat gene on through two different receptors. organism: Mouse tissue_or_cell_type: Brown fat and skeletal muscle experimental_model: Cloning of PGC-1 from a brown fat cDNA library with ectopic expression in white adipose cells limitations: The founding description of the coactivator. Ectopic expression shows sufficiency in white fat cells; it does not establish the size of the contribution in vivo. exposure: Cold exposure of mice; ectopic PGC-1 expression evidence_span: {"source_cache": "artifacts/cold-research/9529258.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf", "start_char": 0, "end_char": 842, "text_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf"} [cold-p9529258] A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. (1998). https://pubmed.ncbi.nlm.nih.gov/9529258/ DOI: 10.1016/s0092-8674(00)81410-5