This Article Full Text Full Text (PDF) All Versions of this Article: 145/4/1625    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ortiga-Carvalho, T. M. Articles by Wondisford, F. E. Search for Related Content PubMed PubMed Citation Articles by Ortiga-Carvalho, T. M. Articles by Wondisford, F. E. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB LIOTHYRONINE PROPYL THIOURACIL

Thyroid Hormone Resistance in the Heart: Role of the Thyroid Hormone Receptor ß Isoform

Department of Medicine (T.M.O.-C., K.H., R.C., R.M.L., F.E.W.), Pritzker School of the Medicine, The University of Chicago, Chicago, Illinois 60637; Instituto de Biofísica Carlos Chagas Filho (T.M.O.-C., C.C.P.-M.), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21949-900, Brazil; and Department of Cardiology (D.G.), University of Illinois at Chicago, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Fredric E. Wondisford, M.D., Department of Medicine, MC1027, 5841 South Maryland Avenue, Chicago, Illinois 60637. E-mail: fwondisf{at}medicine.bsd.uchicago.edu.

Several cardiac genes possess thyroid hormone (TH) response elements regulated by TH receptors. Mutation in TR-ß gene causes the human syndrome of resistance to TH, which is characterized by elevated serum concentration of T₄ and T₃ and variable degrees of insensitivity to TH. It is unclear, however, whether a mutant TR-ß could function as a dominant negative in the heart when expressed from the endogenous locus. A well-described resistance to TH (337T) was either introduced into germline of mice (KI-mut) or expressed as a transgene in the heart using a cardiac-specific promoter (KS-mut). Mice were studied at baseline, after 5-propyl-2-thiouracil (PTU) or after PTU and T₃ treatment (PTU + T₃). PTU + T₃ treatment significantly increased left ventricular mass in all groups compared with baseline measurements, although the increase in left ventricular mass was significantly less in KI-mut animals. Baseline heart rates (HRs) were similar in wild-type (WT) and KI-mut but were lower in KS-mut animals. After TH deprivation (PTU), HR decreased in WT and KI-mut animals; similarly, HR increased in WT and KI-mut after PTU + T₃. In contrast, HR in KS-mut animals did not change after either treatment. Except for cardiac hypertrophy, the presence of a germline TR-ß mutation had surprisingly little effect on cardiac function.

This article has been cited by other articles:

				N. E. Buroker, M. E. Young, C. Wei, K. Serikawa, M. Ge, X.-H. Ning, and M. A. Portman The dominant negative thyroid hormone receptor beta-mutant {Delta}337T alters PPAR{alpha} signaling in heart Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E453 - E460. [Abstract] [Full Text] [PDF]