Molecular and Cellular Endocrinology 226 (2004) 19–26 Thyroid hormone stimulates myoglobin gene expression in rat cardiac muscle Gisele Giannocco, Rosangela A. DosSantos, Maria Tereza Nunes ∗ Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S˜ ao Paulo, 05508-900 S˜ ao Paulo, SP, Brazil Received 8 June 2004; received in revised form 14 July 2004; accepted 16 July 2004 Abstract T 3 increases the heart activity, O 2 consumption and the reactive O 2 species production. Myoglobin (Mb) is highly expressed in the heart, where it facilitates O 2 diffusion, mitochondrial respiration, and scavenges reactive O 2 species. Here we investigate, by dose–response (0.3–100 g/100 g BW, i.p., 5 days) and time-course studies (100 g/100 g BW, i.v., from 0.5 to 24 h), whether T 3 affects the Mb mRNA and protein expression in atrium (A) and ventricle (V), by Northern and Western blot. We show that the Mb gene is controlled by T 3 in A and V, as indicated by Mb mRNA and protein content decrease in thyroidectomized (Tx) rats, and restoration by T 3 treatment. In the A, the different doses of T 3 induced the Mb mRNA and protein recovery to the euthyroid levels; in the time-course study, this occurred only with the protein levels. In the V, T 3 progressively increased the Mb mRNA above the euthyroid levels at a dose of 25 g/100 g BW; higher doses decreased it to the euthyroid levels. Mb protein increased only to the euthyroid levels at all T 3 doses injected. The time-course study showed a progressive increase in the ventricular Mb mRNA and protein, which exceeded the euthyroid levels from 6 to 24 h, and at 2 and 6 h of the T 3 treatment, respectively. We conclude that heart Mb gene expression is influenced by thyroid status. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Myoglobin expression; Thyroid hormone; Cardiac muscle; Hyperthyroidism; Hypothyroidism 1. Introduction Many of the known cellular effects of thyroid hormone result from its interaction with nuclear receptors (TRs) bound to DNA elements of particular genes, a mechanism by which T 3 either promotes or inhibits gene transcription (Glass and Holloway, 1990; Samuels et al., 1989; Shupnik et al., 1985). The presence of specific TR interacting factors and different TR isoforms expressed in a tissue specific manner provides the basis for differential action of T 3 (Brent et al., 1991; Lazar, 1993). More recently, extranuclear effects of thyroid hormone have also been reported, however, the mechanisms involved in those actions are still not well understood (Davis and Davis, 2002). Cardiac muscle is an important target for thyroid hormone. Thyroid hormone increases the transcriptional rate of rat al- ∗ Corresponding author. Tel.: +55 11 3091-7431/7465; fax: +55 11 3091 7285. E-mail address: mtnunes@fisio.icb.usp.br (M.T. Nunes). pha cardiac myosin heavy chain (-MHC) and sarcoplasmic reticulum Ca + ATPases (SERCA 2) while decreases the tran- scription of MHC beta genes, leading to an increased speed of muscle contraction and relaxation and, as a consequence to an increased ATP consumption and synthesis (Samuels et al., 1989; Haddad et al., 1998; Rohrer and Dillmann, 1988). Thyroid hormone also increases the expression of  adrener- gic receptors in this tissue, rendering the cardiac muscle more sensitive to catecholamines, which accounts for the inotropic effects of T 3 in the tissue (Williams et al., 1977; Ojamaa et al., 2000). Increase in the activity of mitochondrial enzymes in rat heart homogenates, induced by thyroid hormone has also been documented (Paradies et al., 1994). On the other hand, hypothyroidism severely alters these properties and trans- forms the rodent heart into a hypokinetic state (Dillmann, 1993, 1996; Haddad et al., 1998). The marked increase in cardiac muscle activity induced by T 3 leads to an enhanced O 2 consumption as well as to reactive O 2 species production (Asayama et al., 1987), and raises the question if the aerobic potential of the heart remains 0303-7207/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2004.07.007