{"id":"25b686ed-000b-5220-91b2-c55375b8fe28","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-dio2-thyroid-sympathetic-synergy","predicate":"is_required_in_assay_for","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d18c5b80-b598-591d-afc6-ae772ecca1ee","mechanism_event_label":"Two receptors need different amounts of hormone, and only local production reaches the hungrier one.","subject":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"object":{"id":"d2721ef8-bdb4-596c-9744-d20b521e1659","slug":"bat-thermogenesis","display_name":"Brown adipose tissue thermogenesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d18c5b80-b598-591d-afc6-ae772ecca1ee","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-dio2-thyroid-sympathetic-synergy-event","event_type":"biochemical_relationship","label":"Two receptors need different amounts of hormone, and only local production reaches the hungrier one.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"012e6f8c-edb7-5962-bdc9-a075c7742137","slug":"thrb","display_name":"Thyroid hormone receptor beta","entity_type_key":"protein"},"role":"comparator_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fc93f0af-2123-58b6-bb7a-ff800479799a","slug":"dio2","display_name":"DIO2","entity_type_key":"protein"},"role":"supplying_enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d2721ef8-bdb4-596c-9744-d20b521e1659","slug":"bat-thermogenesis","display_name":"Brown adipose tissue thermogenesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"cold-water-immersion","display_name":"Cold water immersion","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Two receptors need different amounts of hormone, and only local production reaches the hungrier one.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. 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Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone.\nexposure: Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection\nevidence_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\"}\n[cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. 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