title: The targeted inactivation of TRβ gene in thyroid follicular cells suggests a new mechanism of regulation of thyroid hormone production.
abstract: Thyroid epithelial cells, or thyrocytes, express functional thyroid hormone receptors but no precise role has yet been assigned to either TRα or TRβ in the thyroid gland. In this study, we analyzed the impact of inactivating the TRβ gene in the thyroid of mice. First, we generated a mouse line named Thyr-Cre, expressing the Cre recombinase under the control of the thyroglobulin gene promoter, which led to a complete recombination of floxed genes in thyrocytes. Thyr-Cre mice were then crossed with TRβ floxed mice (TRβ(flox/flox)) to obtain a thyrocyte-selective deletion of TRβ. Thyr-TRβ(-/-) mice were characterized by a decrease in the size and functional activity of the thyroid gland. These alterations were associated with a decrease in plasma TSH concentration. Surprisingly, Thyr-TRβ(-/-) displayed elevated serum T(4) and rT(3) concentrations with no significant change in serum T(3) levels. Their intrathyroidal free T(4) and rT(3) contents were also elevated, whereas the ratio of serum T(4) to thyroid free T(4) was decreased by comparison with wild-type littermates. Also, within the thyroid, deiodinases D1 and D2 were reduced as well as the expression levels of genes encoding monocarboxylate transporters (Mct8 and Mct10). Such a decrease in intrathyroidal deiodination of T(4) and in the expression of genes encoding thyroid hormone transporters may contribute to the primary overproduction of T(4) observed in Thyr-TRβ(-/-) mice. In conclusion, these data show that the control of thyroid hormone production involves not only TRβ-dependent mechanisms acting at the level of hypothalamus and pituitary but also TRβ-dependent mechanisms acting at the thyroid level.
authors.affiliation: Inserm Unité 1052 (S.S.-R., F.B.-C., B.R.), Lyon, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 5286 (S.S.-R., F.B.-C., B.R.), Lyon, France; Université Claude Bernard Lyon 1 (S.S.-R., L.B., F.B.-C., B.R.), Faculté de Médecine Lyon-Est-Site Laennec, Lyon Cedex 08, F-69372 France; Instituto de Investigaciones Biomedicas (Consejo Superior de Investigaciones Científicas-Universidad Autonoma Madrid) (M.-J.O.), Madrid, M-28029 Spain; and Institut de Génomique Fonctionnelle de Lyon (A.C., F.F., J.S.), Lyon, F-69007 France.
authors.forename: Samia
authors.initials: S
authors.lastname: Selmi-Ruby
authors.forename: Lamia
authors.initials: L
authors.lastname: Bouazza
authors.forename: Maria-Jesus
authors.initials: MJ
authors.lastname: Obregon
authors.forename: Aude
authors.initials: A
authors.lastname: Conscience
authors.forename: Frédéric
authors.initials: F
authors.lastname: Flamant
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.forename: Françoise
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: Bernard
authors.initials: B
authors.lastname: Rousset
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D027501:Monocarboxylic Acid Transporters; D011401:Promoter Regions, Genetic; D027981:Symporters; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics* / Q000378:metabolism; D013963:Thyroid Hormones / Q000096:biosynthesis*; D013972:Thyrotropin / Q000097:blood*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D013972:Thyrotropin; D000097564:Iodothyronine Deiodinase Type II; C484257:Slc16a2 protein, mouse