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

Esaki, Takanori, Hideyo Suzuki, Michelle Cook, Kazuaki Shimoji, Sheue-Yann Cheng, Louis Sokoloff, and Jacques Nunez. Cardiac glucose utilization in mice with mutated and -thyroid hormone receptors. Am J Physiol Endocrinol Metab 287: E1149–E1153, 2004. First published August 10, 2004; doi:10.1152/ajpendo.00078. 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 ) 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 (CMRGlc) in TR PV/PV mice and markedly reduced CMRGlc, 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 (HMRGlc) in both the TR PV/PV and TR PV/ mutants. Compared with values in normal wild-type mice, HMRGlc 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.