Kinetics of Thyroxine (T₄) and Triiodothyronine (T₃) Transport in the Isolated Rat Heart

Abstract

Thyroid hormones are the iodized derivatives of the amino acid tyrosine and are synthesized by the thyroid gland. Thyroxine (T 4 ) and triiodothyronine (T 3 ) regulate the processes of general metabolism (oxidative phosphorylation), growth, development and specific gene expression (Oppenheimer & Schwartz, 1987;Samuels, 1988). About 90 % of the thyroid production is T 4 while 10 % is T 3 . It is thought that T 4 has little, if any, biological activity, and it is considered as a prohormone, which becomes activated upon conversion into T 3 in peripheral tissues. About 80 % of the daily T 3 production is generated via this process while the remaining 20 % is directly secreted from the thyroid (Hennemann, 1987).To respond to thyroid hormone signals, cells have to contain specific thyroid hormone receptors (nuclear proteins) and thyroid hormone response elements (TRE) (specific DNA sequences upstream of regulated genes) (Brent et al. 1989). Thyroid hormone exerts its actions at a cellular level by binding to specific thyroid hormone receptor (TR) and binding of TR to TRE, in order to stimulate or inhibit the rate of transcription of specific genes (Franklyn & Gammage, 1996). Up to now, two major classes of thyroid hormone nuclear receptors have been described: thyroid hormone receptor-a (TRa) and thyroid hormone receptor-b (TRb) (Franklyn & Gammage, 1996;Nagaya et al. 1996). Several isoforms (a 1 , a 2 , a 3 , b 1 and b 2 ) are created by alternative splicing of TRa and TRb gene (Nagaya et al. 1996) and they display differences in terms of their tissue distribution and functional properties (Franklyn & Gammage, 1996). It has been shown that TRa 1 , TRa 2 and TRb 1 are expressed in the myocardium, and that TRa 1 and TRb 1 bind the ligand (thyroid hormone), while TRa 2 is non-ligand binding variant which may exert a 'dominant negative' influence on the action of a 1 and b 1 thyroid hormone receptor proteins (Brent et al. 1991;Franklyn & Gammage, 1996).Thyroid hormones have strong effects on the heart and circulation. It is considered that thyroid hormones perform direct and indirect actions on the heart. Thus, direct thyroid hormone actions on the heart involve regulation of transcription of a number of functionally relevant genes in the myocardium (nuclear mechanism). These include the myosin heavy chain contractile proteins (Ojamaa & Klein, 1993; Dubus et al. 1993), Na + ,K + -ATPase (Liu et al. 1993;Huang et al. 1994), Ca 2+ -ATPase and phospholamban (Kimura et al. 1994), which modulate the activity of calcium translocator (Klein & Ojamaa, 1996). But some effects, like the thyroid hormone effects on calcium uptake by the myocyte, are mediated by direct action on the plasma The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of 125 Kinetics of thyroxine (T 4 ) and triiodothyronine (T 3 ) transport in the isolated rat heart

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