Chronic cardiac-specific thyrotoxicosis increases myocardial β-adrenergic responsiveness

Suzy D. Carvalho-Bianco, Brian W. Kim, Julie X. Zhang, John W. Harney, Rogério S. Ribeiro, Balazs Gereben, Antonio C. Bianco, Ulrike Mende, P. Reed Larsen

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Whereas many cardiac symptoms of thyrotoxicosis resemble those of the hyperadrenergic state, circulating catecholamines are reduced or normal in this condition. To test the hypothesis that the thyrotoxic heart is hypersensitive to catecholamines, we studied β-adrenergic signaling in a transgenic (TG) mouse in which the human type 2 iodothyronine deiodinase (D2) gene is expressed in myocardium. Because D2 converts T4 to T3, the active form of thyroid hormone, the D2 TG mouse exhibits mild, chronic thyrotoxicosis that is limited to the myocardium. In the current study, we determined that cAMP accumulation in response to either norepinephrine or forskolin treatment was increased in isolated ventricular myocardiocytes and membrane-enriched fractions prepared from these D2 TG hearts as compared with wild type. This increase in adenylyl cyclase (AC) Vmax could not be explained by changes in AC isoform expression or changes in the long or short forms of stimulatory G-protein Gsα, which were approximately 10% decreased in D2 TG membranes. However, Western analysis and ADP-ribosylation studies suggest that the increase in ACVmax is mediated by a decrease in the expression of inhibitory G proteins (Giα-3 and/or Goα). These data suggest that cardiac thyrotoxicosis leads to increased β-adrenergic responsiveness of cardiomyocytes via alterations in the regulatory G-protein elements of the AC membrane complex.

Original languageEnglish (US)
Pages (from-to)1840-1849
Number of pages10
JournalMolecular Endocrinology
Issue number7
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


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