Thyroid hormone increases the Ca2+-ATPase activity of the sarcoplasmic reticulum (SR) in skeletal muscle, thereby increasing the energy-turnover associated with Ca2+-cycling during contraction and rest. The fast-muscle isoform of the Ca2+-ATPase (SERCA1) and the slow-muscle isoform (SERCA2a), are encoded by two genes that are transcriptionally regulated by T3. The SERCA1 isoform can be expressed to considerably higher levels than the SERCA2a isoform. The stimulation of transcription of the SERCA1 gene by T3 is mediated by two thyroid hormone response elements, located in the promoter of this gene. The intracellular [Ca2+] can modulate the effect of T3. The increase in SR Ca2+-ATPase activity seen when T3-levels rise above normal, results from the induction of SERCA1 expression in slow muscle fibers. Concomitant high levels of Ca2+-ATPase activity are associated with down-regulation of SERCA2a expression in these fibers. The observed T3-dependent increase in SERCA1 expression and associated Ca2+-ATPase activity will increase the overall metabolic rate of the organism significantly under normal conditions, because of the high average level of contractile activity of slow fibers. Given the rise in serum T3-levels during prolonged cold exposure, these data suggest that fiber-specific stimulation of SERCA1 expression contributes to the thermogenic response in non-shivering thermogenesis. This mechanism may be particularly relevant in larger mammals, which have a relatively high percentage of slow fibers in skeletal muscle, and which need to rely on tissues other than brown fat for the generation of extra heat.
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April 01 2001
Mechanism of Thyroid-Hormone Regulated Expression of the SERCA Genes in Skeletal Muscle: Implications for Thermogenesis
Walter S. Simonides;
Walter S. Simonides
1Institute for Cardiovascular Research (ICaR-VU), Vrije Universiteit, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands
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Marc H. M. Thelen;
Marc H. M. Thelen
1Institute for Cardiovascular Research (ICaR-VU), Vrije Universiteit, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands
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C. Gerard van der Linden;
C. Gerard van der Linden
1Institute for Cardiovascular Research (ICaR-VU), Vrije Universiteit, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands
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Alice Muller;
Alice Muller
1Institute for Cardiovascular Research (ICaR-VU), Vrije Universiteit, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands
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Cornelis van Hardeveld
Cornelis van Hardeveld
1Institute for Cardiovascular Research (ICaR-VU), Vrije Universiteit, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands
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Publisher: Portland Press Ltd
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 2001 Plenum Publishing Corporation
2001
Biosci Rep (2001) 21 (2): 139–154.
Citation
Walter S. Simonides, Marc H. M. Thelen, C. Gerard van der Linden, Alice Muller, Cornelis van Hardeveld; Mechanism of Thyroid-Hormone Regulated Expression of the SERCA Genes in Skeletal Muscle: Implications for Thermogenesis. Biosci Rep 1 April 2001; 21 (2): 139–154. doi: https://doi.org/10.1023/A:1013692023449
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