Thyroid hormone receptor α and regulation of type 3 deiodinase.

Mice deficient in thyroid hormone receptor alpha (TRalpha) display hypersensitivity to thyroid hormone (TH), with normal serum TSH but diminished serum T(4). Our aim was to determine whether altered TH metabolism played a role in this hypersensitivity. TRalpha knockout (KO) mice have lower levels of...

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Autores: Barca-Mayo, Olga, Liao, Xiao-Hui, Alonso Sampedro, Manuela, Di Cosmo, Caterina, Hernandez, Arturo, Refetoff, Samuel, Weiss, Roy E
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/5896
Acceso en línea:http://hdl.handle.net/20.500.11940/5896
Access Level:acceso abierto
Palabra clave:Male
Animals
Mice
Cells, Cultured
Gene Expression Regulation
Polymerase Chain Reaction
Promoter Regions, Genetic
Mice, Knockout
Triiodothyronine
RNA, Messenger
Iodide Peroxidase
Thyroid Hormone Receptors alpha
Thyroxine
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oai_identifier_str oai:runa.sergas.gal:20.500.11940/5896
network_acronym_str ES
network_name_str España
repository_id_str
spelling Thyroid hormone receptor α and regulation of type 3 deiodinase.Barca-Mayo, OlgaLiao, Xiao-HuiAlonso Sampedro, ManuelaDi Cosmo, CaterinaHernandez, ArturoRefetoff, SamuelWeiss, Roy EMaleAnimalsMiceCells, CulturedGene Expression RegulationPolymerase Chain ReactionPromoter Regions, GeneticMice, KnockoutTriiodothyronineRNA, MessengerIodide PeroxidaseThyroid Hormone Receptors alphaThyroxineMice deficient in thyroid hormone receptor alpha (TRalpha) display hypersensitivity to thyroid hormone (TH), with normal serum TSH but diminished serum T(4). Our aim was to determine whether altered TH metabolism played a role in this hypersensitivity. TRalpha knockout (KO) mice have lower levels of rT(3), and lower rT(3)/T(4) ratios compared with wild-type (WT) mice. These alterations could be due to increased type 1 deiodinase (D1) or decreased type 3 deiodinase (D3). No differences in D1 mRNA expression and enzymatic activity were found between WT and TRalphaKO mice. We observed that T(3) treatment increased D3 mRNA in mouse embryonic fibroblasts obtained from WT or TRbetaKO mice, but not in those from TRalphaKO mice. T(3) stimulated the promoter activity of 1.5 kb 5'-flanking region of the human (h) DIO3 promoter in GH3 cells after cotransfection with hTRalpha but not with hTRbeta. Moreover, treatment of GH3 cells with T(3) increased D3 mRNA after overexpression of TRalpha. The region necessary for the T(3)-TRalpha stimulation of the hD3 promoter (region -1200 to -1369) was identified by transfection studies in Neuro2A cells that stably overexpress either TRalpha or TRbeta. These results indicate that TRalpha mediates the up-regulation of D3 by TH in vitro. TRalphaKO mice display impairment in the regulation of D3 by TH in both brain and pituitary and have reduced clearance rate of TH as a consequence of D3 deregulation. We conclude that the absence of TRalpha results in decreased clearance of TH by D3 and contributes to the TH hypersensitivity.2011info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.11940/5896reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Inglésinfo:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/58962026-06-12T08:40:47Z
dc.title.none.fl_str_mv Thyroid hormone receptor α and regulation of type 3 deiodinase.
title Thyroid hormone receptor α and regulation of type 3 deiodinase.
spellingShingle Thyroid hormone receptor α and regulation of type 3 deiodinase.
Barca-Mayo, Olga
Male
Animals
Mice
Cells, Cultured
Gene Expression Regulation
Polymerase Chain Reaction
Promoter Regions, Genetic
Mice, Knockout
Triiodothyronine
RNA, Messenger
Iodide Peroxidase
Thyroid Hormone Receptors alpha
Thyroxine
title_short Thyroid hormone receptor α and regulation of type 3 deiodinase.
title_full Thyroid hormone receptor α and regulation of type 3 deiodinase.
title_fullStr Thyroid hormone receptor α and regulation of type 3 deiodinase.
title_full_unstemmed Thyroid hormone receptor α and regulation of type 3 deiodinase.
title_sort Thyroid hormone receptor α and regulation of type 3 deiodinase.
dc.creator.none.fl_str_mv Barca-Mayo, Olga
Liao, Xiao-Hui
Alonso Sampedro, Manuela
Di Cosmo, Caterina
Hernandez, Arturo
Refetoff, Samuel
Weiss, Roy E
author Barca-Mayo, Olga
author_facet Barca-Mayo, Olga
Liao, Xiao-Hui
Alonso Sampedro, Manuela
Di Cosmo, Caterina
Hernandez, Arturo
Refetoff, Samuel
Weiss, Roy E
author_role author
author2 Liao, Xiao-Hui
Alonso Sampedro, Manuela
Di Cosmo, Caterina
Hernandez, Arturo
Refetoff, Samuel
Weiss, Roy E
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Male
Animals
Mice
Cells, Cultured
Gene Expression Regulation
Polymerase Chain Reaction
Promoter Regions, Genetic
Mice, Knockout
Triiodothyronine
RNA, Messenger
Iodide Peroxidase
Thyroid Hormone Receptors alpha
Thyroxine
topic Male
Animals
Mice
Cells, Cultured
Gene Expression Regulation
Polymerase Chain Reaction
Promoter Regions, Genetic
Mice, Knockout
Triiodothyronine
RNA, Messenger
Iodide Peroxidase
Thyroid Hormone Receptors alpha
Thyroxine
description Mice deficient in thyroid hormone receptor alpha (TRalpha) display hypersensitivity to thyroid hormone (TH), with normal serum TSH but diminished serum T(4). Our aim was to determine whether altered TH metabolism played a role in this hypersensitivity. TRalpha knockout (KO) mice have lower levels of rT(3), and lower rT(3)/T(4) ratios compared with wild-type (WT) mice. These alterations could be due to increased type 1 deiodinase (D1) or decreased type 3 deiodinase (D3). No differences in D1 mRNA expression and enzymatic activity were found between WT and TRalphaKO mice. We observed that T(3) treatment increased D3 mRNA in mouse embryonic fibroblasts obtained from WT or TRbetaKO mice, but not in those from TRalphaKO mice. T(3) stimulated the promoter activity of 1.5 kb 5'-flanking region of the human (h) DIO3 promoter in GH3 cells after cotransfection with hTRalpha but not with hTRbeta. Moreover, treatment of GH3 cells with T(3) increased D3 mRNA after overexpression of TRalpha. The region necessary for the T(3)-TRalpha stimulation of the hD3 promoter (region -1200 to -1369) was identified by transfection studies in Neuro2A cells that stably overexpress either TRalpha or TRbeta. These results indicate that TRalpha mediates the up-regulation of D3 by TH in vitro. TRalphaKO mice display impairment in the regulation of D3 by TH in both brain and pituitary and have reduced clearance rate of TH as a consequence of D3 deregulation. We conclude that the absence of TRalpha results in decreased clearance of TH by D3 and contributes to the TH hypersensitivity.
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.11940/5896
url http://hdl.handle.net/20.500.11940/5896
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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