Different functions for the thyroid hormone receptors TR|[alpha]| and TR|[beta]| in the control of thyroid hormone production and post-natal development

doi:doi:10.1093/emboj/18.3.623

Article

The EMBO Journal (1999) 18, 623 - 631
doi:10.1093/emboj/18.3.623

Different functions for the thyroid hormone receptors TR and TR in the control of thyroid hormone production and post-natal development

Karine Gauthier^1,⁵, Olivier Chassande^1,⁵, Michela Plateroti¹, Jean-Paul Roux², Claude Legrand¹, Bertrand Pain¹, Bernard Rousset³, Roy Weiss⁴, Jacqueline Trouillas³ and Jacques Samarut¹

CNRS UMR 49-INRA LA 913, Ecole Normale Supérieure, 46 allée d'Italie, 69364 Lyon cedex, France
INSERM U403, Hopital Edouard Herriot, Lyon, France
INSERM U369, Faculté de Medecine, RTH Laennec, Lyon, France
Thyroid Unit, MC 3090, University of Chicago, Chicago IL 60637, USA
K.Gauthier and O.Chassande contributed equally to this work

Correspondence to:

Olivier Chassande, E-mail: ochassan@ens-lyon.fr

Received 26 October 1998; Accepted 25 November 1998

The biological activities of thyroid hormones are thought to be mediated by receptors generated by the TR and TR loci. The existence of several receptor isoforms suggests that different functions are mediated by specific isoforms and raises the possibility of functional redundancies. We have inactivated both TR and TR genes by homologous recombination in the mouse and compared the phenotypes of wild-type, and single and double mutant mice. We show by this method that the TR beta receptors are the most potent regulators of the production of thyroid stimulating hormone (TSH). However, in the absence of TR, the products of the TR gene can fulfill this function as, in the absence of any receptors, TSH and thyroid hormone concentrations reach very high levels. We also show that TR beta , in contrast to TR alpha , is dispensable for the normal development of bone and intestine. In bone, the disruption of both TR and TR genes does not modify the maturation delay observed in TR^-/- mice. In the ileum, the absence of any receptor results in a much more severe impairment than that observed in TR^-/- animals. We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions.