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CELLULAR AND MITOCHONDRIAL METABOLISM

H9c2 cardiomyoblasts produce thyroid hormone

¹Department of Pathology, ²Department of Physiology, ³Department of Nuclear Medicine, and ⁴Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands; ⁵Unité 486 Institut National de la Santé et de la Recherche Médicale, Université Paris 11, Châtenay-Malabry Cedex, France; ⁶Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands; ⁷Laboratory of Pediatric Endocrinology, Academic Medical Center, Amsterdam, The Netherlands; ⁸Department of Blood-Cell Research, Sanquin Research, Amsterdam, The Netherlands; ⁹Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands; and ¹⁰IcaR-VU, VU University Medical Center, Amsterdam, The Netherlands

Submitted 27 July 2007 ; accepted in final form 3 March 2008

Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of ¹²⁵I, we found that ¹²⁵I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, ¹²⁵I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.

DUOX; cardiomyocyte; ischemia; heart failure

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