{"doi":"10.1152/ajpendo.00226.2002","title":"Specificity of thyroid hormone receptor subtype and  steroid receptor coactivator-1 on thyroid hormone action","abstract":"<jats:p> Isoforms of the thyroid hormone receptor ( TR) α and TRβ genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRα and SRC-1, as well as in TRβ and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRα or TRβ, SRC-1 is important for normal growth; 2) SRC-1 modulates TRα and TRβ effects on heart rate; 3) two new TRβ-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRα-deficient mice. </jats:p>","journal":"American Journal of Physiology-Endocrinology and Metabolism","year":2003,"id":672416,"datarank":0.5806801516361837,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"self_citation_contribution":0.5806801516361837,"citation_network_contribution":0.0,"self_endowment_contribution":0.5806801516361837,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1756849,"name":"Olivier Chassande","orcid":null,"position":1,"is_corresponding":false},{"id":1256632,"name":"Karine Gauthier","orcid":"0000-0003-2961-6119","position":2,"is_corresponding":false},{"id":1756850,"name":"Jacques Samarut","orcid":null,"position":3,"is_corresponding":false},{"id":112616,"name":"Jianming Xu","orcid":null,"position":4,"is_corresponding":false},{"id":1756853,"name":"Bert W. O′Malley","orcid":null,"position":5,"is_corresponding":false},{"id":377338,"name":"Roy E. Weiss","orcid":"0000-0003-3671-0621","position":6,"is_corresponding":false},{"id":414416,"name":"Peter M. Sadow","orcid":"0000-0003-1036-6367","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Specificity of thyroid hormone receptor subtype and  steroid receptor coactivator-1 on thyroid hormone action","abstract":"<jats:p> Isoforms of the thyroid hormone receptor ( TR) α and TRβ genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRα and SRC-1, as well as in TRβ and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRα or TRβ, SRC-1 is important for normal growth; 2) SRC-1 modulates TRα and TRβ effects on heart rate; 3) two new TRβ-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRα-deficient mice. </jats:p>","is_dataset_classified":null,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12388168","pmcid":null,"openalex_id":"https://openalex.org/W2127781891","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK-58242","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"HD-078587","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK-58281","title":null}],"total_grants":3,"fwci":3.5972,"citation_percentile":0.93657492,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2015,"count":2},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2023,"count":1},{"year":2024,"count":4},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.physiology.org/doi/pdf/10.1152/ajpendo.00226.2002","host_type":"publisher"},{"url":"https://doi.org/10.1152/ajpendo.00226.2002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12388168","host_type":"repository"}],"fields_of_study":["Thyroid Disorders and Treatments","Estrogen and related hormone effects","Growth Hormone and Insulin-like Growth Factors","Animals","Energy Metabolism","Gene Expression","Genotype","Heart Rate","Histone Acetyltransferases","Leptin","Liver","Mice","Mice, Inbred C57BL","Mice, Knockout","Nuclear Receptor Coactivator 1","Oligonucleotide Array Sequence Analysis","Receptors, Thyroid Hormone","Response Elements","Reverse Transcriptase Polymerase Chain Reaction","Thyroid Gland","Thyroid Hormone Receptors alpha","Thyroid Hormone Receptors beta","Thyroid Hormones","Thyrotropin","Thyroxine","Transcription Factors","Triiodothyronine","Weight Gain"],"mesh_terms":["Animals","Energy Metabolism","Genotype","Heart Rate","Liver","Mice, Inbred C57BL","Receptors, Thyroid Hormone","Thyroid Gland","Thyroid Hormones","Thyrotropin","Thyroxine","Transcription Factors","Triiodothyronine","Weight Gain","Gene Expression","Mice, Knockout","Reverse Transcriptase Polymerase Chain Reaction","Response Elements","Oligonucleotide Array Sequence Analysis","Leptin","Thyroid Hormone Receptors alpha","Thyroid Hormone Receptors beta","Mice","Histone Acetyltransferases","Nuclear Receptor Coactivator 1"],"keywords":["Thyroid hormone receptor","Thyroid hormone receptor beta","Nuclear receptor","Thyroid hormone receptor alpha","Coactivator","Endocrinology","Internal medicine","Biology","Receptor","Proto-oncogene tyrosine-protein kinase Src","Thyroid","Hormone receptor","Transcription factor","Medicine","Biochemistry","Gene","Cancer","Non-programmatic"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T09:02:01.036215Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}