title: Gene expression of T3-regulated genes in a mouse model of the human thyroid hormone resistance.
abstract: OBJECTIVE
  To understand how thyroid hormone (TH) regulates tissue-specific gene expression in patients with the syndrome of resistance to TH (RTHβ), we used a mouse model that replicates the human RTHβ, specifically the ∆337T mutation in the thyroid hormone receptor β (THRβ).
  
  
  METHODS
  We investigated the expression of key TH target genes in the pituitary and liver of TRβ∆337Tand wild type THRβ mice by qPCR before and after a T3suppression test consisting of the administration of increasing concentrations of T3to hypothyroid mice.
  
  
  RESULTS
  Pituitary Tshb and Cga expression decreased and Gh expression increased in TRβ∆337Tmice after T3suppression. The stimulation of positively regulated TH genes was heterogeneous in the liver. Levels of liver Me1 and Thsrp were elevated in TRβ∆337Tmice after T3administration. Slc16a2 and Gpd2 did not respond to T3stimulation in the liver of TRβ∆337Tmice whereas Dio1 response was lower than that observed in WT mice. Moreover, although Chdh and Upd1 genes were negatively regulated in the liver, the expression of these genes was elevated after T3suppression. We did not observe significant changes in THRα expression in the liver and pituitary, while THRβ levels were diminished in the pituitary and increased in the liver.
  
  
  CONCLUSIONS
  Using a model expressing a THRβ unable to bind T3, we showed the expression pattern of liver negative and positive regulated genes by T3.
authors.affiliation: Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: L A
authors.initials: LA
authors.lastname: Santiago
authors.affiliation: Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: L C
authors.initials: LC
authors.lastname: Faustino
authors.affiliation: Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: G F
authors.initials: GF
authors.lastname: Pereira
authors.affiliation: Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: G E
authors.initials: GE
authors.lastname: Imperio
authors.affiliation: Laboratório de Endocrinologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: C C
authors.initials: CC
authors.lastname: Pazos-Moura
authors.affiliation: Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: F E
authors.initials: FE
authors.lastname: Wondisford
authors.affiliation: Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: F F
authors.initials: FF
authors.lastname: Bloise
authors.affiliation: Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: taniaort@biof.ufrj.br.
authors.forename: T M
authors.initials: TM
authors.lastname: Ortiga-Carvalho
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010902:Pituitary Gland / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D014284:Triiodothyronine; D013006:Growth Hormone
keywords: Gene expression; Liver; Thyroid hormone receptor