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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/E1149    most recent 00078.2004v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Esaki, T. Articles by Nunez, J. Search for Related Content PubMed PubMed Citation Articles by Esaki, T. Articles by Nunez, J.

Cardiac glucose utilization in mice with mutated - and -thyroid hormone receptors

¹Laboratory of Cerebral Metabolism, National Institute of Mental Health; ³Positron Emission Department, Clinical Center; and ²Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Submitted 19 February 2004 ; accepted in final form 16 July 2004

Abnormal thyroid function is usually associated with altered cardiac function. Mutations in the thyroid hormone (TH)-binding region of the TH -receptor (TR) that eliminate its TH-binding ability lead to the thyroid hormone resistance syndrome (RTH) in humans, which is characterized by high blood TH levels, goiter, hyperactivity, and tachycardia. Mice with "knock-in" mutations in the TH -receptor (TR) or TR that remove their TH-binding ability have been developed, and those with the mutated TR (TR^PV/PV) appear to provide a model for RTH. These two types of mutants show different effects on cerebral energy metabolism, e.g., negligible change in glucose utilization (CMR_Glc) in TR^PV/PV mice and markedly reduced CMR_Glc, like that found in cretinous rats, in the mice (TR^PV/+) with the knock-in mutation of the TR gene. Studies in knockout mice have indicated that the TR may also influence heart rate. Because mutations in both receptor genes appear to affect some parameters of cardiac function and because cardiac functional activity and energy metabolism are linked, we measured heart glucose utilization (HMR_Glc) in both the TR^PV/PV and TR^PV/+ mutants. Compared with values in normal wild-type mice, HMR_Glc was reduced (–77 to –95%) in TR^PV/+ mutants and increased (87 to 340%) in TR^PV/PV mutants, the degree depending on the region of the heart. Thus the TR^PV/+ and TR^PV/PV mutations lead, respectively, to opposite effects on energy metabolism in the heart that are consistent with the bradycardia seen in hypothyroidism and the tachycardia associated with hyperthyroidism and RTH.

heart; thyroid hormone resistance syndrome; glucose metabolism; 2-deoxyglucose