Summary
Experimental hyperthyroidism induced in rats by daily injections of 3,3′,5,5′-tetraiode-l-thyroxine (0.5 mg/kg i.p.) for 14 days resulted in a significant increase in heart weight and heart weight/body weight ratio. Hemodynamic and morphological studies were performed in one group. Thyroxine-treated rats showed a characteristic cardiovascular hyperdynamic state, such as tachycardia and augmented rate of contraction, but no evidence of heart failure such as elevated end-diastolic pressures. The cardiac cells in hyperthyroid rats had a significantly larger diameter and more mitochondria than did those of the control rats. In another group the activities of cardiac enzymes involved in energy utilization and liberation were measured biochemically and compared with those of normal controls. Hyperthyroidism resulted in increased specific activity of cytochrome C oxidase and actomyosin ATPase in the myocardium. The specific activity of long-chain acyl-CoA synthetase, carnitine palmityltransferase, carnitine acetyltransferase, malate dehydrogenase and citrate synthase showed a moderate to marked increment, whereas the specific activity of lactate dehydrogenase and pyruvate kinase remained at the control values. These results suggest that in hyperthyroid rat hearts the functions of both energy liberation and utilization systems are enhanced to meet the added workload. Moreover, the increased activity of the enzymes participating in fatty acid metabolism suggest that in thyroxine-induced hypertrophic and hyperdynamic rat hearts, fatty acids contribute more to the energy supply than do carbohydrates.
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Banerjee SK, Kabbas EG, Morkin E (1977) Enzymatic properties of the heavy meromyosin subfragment of cardiac myosin from normal and thyrotoxic rabbits. J Biol Chem 252:6925–6929
Banerjee SK, Morkin E (1977) Actin-activated adenosin triphosphatase activity of normal and N-ethylmaleimide-modified cardiac myosin from normal and thyrotoxic rabbits. Circ Res 41:630–634
Barany M (1967) ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol 50:197–218
Bergmeyer HU, Bernt E (1974) Malate dehydrogenase. In: Bergmeyer HU (ed) Methods of enzymology. Academic Press, Inc, New York London, pp 613–617
Beznak M (1962) Cardiovascular effects of thyroxine treatment in normal rat. Can J Biochem Physiol 40:1647–1654
Bing RJ (1965) Cardiac metabolism Physiol Rev 45:171–213
Bowman RH (1962) The effect of long-chain fatty acids on glucose utilization in the isolated perfused rat heart. Biochem J 84:14
Bremer J, Norum KR (1967) The mechanism of substrate inhibition of palmityl coenzyme A: carnitine palmityltransferase by palmityl coenzyme A. J Biol Chem 242:1744–1748
Buccino RA, Spann JF Jr, Pool PE, Sonnenblick EH, Braunwald E (1967) Influence of the thyroid state on the intrinsic contractile properties and energy stores of the myocardium. J Clin Invest 46:1669–1682
Buchanan JL, Primack MP, Tapley DF (1971) Effect of inhibition of mitochondrial protein synthesisin vitro upon thyroxine stimulation of oxygen consumption. Endocrinology 89:534–537
Cederblad G, Lindstedt S (1972) A method for the determination of carnitine in the picomole range. Clin Chim Acta 37:235–243
Ceriotti G (1955) Determination of nucleic acids in animal tissues. J Biol Chem 214:50–70
Cohen J (1974) Role of endocrine factors in the pathogenesis of cardiac hypertrophy. Circ Res 34–35 (Suppl II), II-49–II-57
Conway G, Heazlitt RA, Fowler NO, Gabel M, Green S (1976) The effect of hyperthyroidism on the sarcoplasmic reticulum and myosin ATPase of dog hearts. J Mol Cell Cardiol 8:39–51
Craft-Cormney C, Hansen JT (1980) Early ultrastructural changes in the myocardium following thyroxine-induced hypertrophy. Virchows Archiv B Cell Path 33:267–273
Davidson DM, Covell JW, Malloch CI, Ross J Jr (1974) Factors influencing indices of left ventricle contractility in the conscious dog. Cardiovasc Res 8:299–312
Evans JR (1964) Importance of fatty acid in myocardial metabolism. Circ Res 14–15 (Suppl II), II-96–II-108
Freedberg AS, Hamolsky MW (1974) Effect of thyroid hormones on certain nonendocrine organ systems. In: Greep RO (ed) Handbook of Physiology, Endocrinology. Am Physiol Soc, Washington DC, sect 7, volume 3, chap 25, pp 435–468
Gemmill CL (1958) Cardiac hypertrophy in rats and mice given 3,3′,5-triiodo-l-thyronine orally. Am J Physiol 195:385–390
Goodkind MJ (1968) Left ventricular myocardial contractile response to aortic constriction in the hyperthyroid guinea pig. Circ Res 22:605–614
Goodkind MJ, Dambach GE, Thyrum PT, Luchi RJ (1974) Effect of thyroxine on ventricular myocardial contractility and ATPase activity in guinea-pigs. Am J Physiol 226:66–72
Goodridge AG, Adelman TG (1976) Regulation of malic enzyme synthesis by insulin, triiodothyronine, and glucagon in liver cells in culture. J Biol Chem 251:3027–3032
Inchiosa MA Jr, Freedberg AS (1963) Influence of thyroid hormones upon cardiac size and actomyosin content. Fed Proc Fed Amer Soc Exp Biol 22:228
Kawamura K, Kashii C, Imamura K (1976) Ultrastructural changes in hypertrophied myocardium of spontaneously hypertensive rats. Jpn Circ J 40:1119–1145
Korecky B, Beznak M (1971) Effect of thyroxine on growth and function of cardiac muscle. In: Alpert NR (ed) Cardiac hypertrophy. Academic Press, New York London, pp 55–64
Lardy HA, Maley GF (1954) Metabolic effects of thyroid hormones in vitro. Recent Prog Horm Res 10:129–155
Lee YP, Lardy HA (1965) Influence of thyroid hormones on L-α-glycerophosphate dehydrogenases and other dehydrogenases in various organs of the rat. J Biol Chem 240:1427–1436
Levey GS (1971) Catecholamine sensitivity, thyroid hormone and the heart: a reevaluation. Am J Med 50:413–420
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
McCallister LP, Brown AL Jr (1965) A quantitative study of myocardial mitochondria in experimental cardiac hypertrophy. Lab Invest 14:692–700
McCallister LP, Page E (1973) Effects of thyroxine on ultrastructure of rat myocardial cells. A stereological study. J Ultrast Res 42:136–155
Neely JR, Bowman RH, Morgan HE (1969) Effects of ventricular pressure development and palmitate on glucose transport. Am J Physiol 216:804–811
Newsholme EA, Randle PJ, Manchester KL (1962) Inhibition of the phosphofructokinase reaction in perfused rat heart by respiration of ketone bodies, fatty acids and pyruvate. Nature 193:270–271
Newsholme EA, Start C (1973) Regulation of fatty acid oxidation. In: Newsholme EA, Start C (eds) Regulation in Metabolism. John Wiley and Sons, New York, pp 298–300
Opie LH (1968) Metabolism of the heart in health and disease. Part I. Amer Heart J 76:685–698
Page E, McCallister LP (1973) Quantitative electron microscopic description of heart muscle cells. Application to normal, hypertrophied and thyroxine-stimulated hearts. Amer J Cardiol 31:172–181
Pande SV, Blanchaer MC (1970) Preferential loss of ATP-dependent long-chain fatty acid activating enzyme in mitochondria prepared using nagarse. Biochim Biophys Acta 202:43–48
Schweitzer ES, Farron F, Knox WE (1972) Distribution of lactate dehydrogenase and its subunits in rat tissues and tumors. Enzyme 14:173–184
Shepherd D, Garland PB (1969) Citrate synthase from rat liver. In: Lowestein JM (ed) Methods in Enzymology. Academic Press, New York London, volume 13, pp 11–16
Shipp JC, Opie LH, Challoner D (1961) Fatty acid and glucose metabolism in the perfused heart. Nature 189:1018–1019
Simon EJ, Shemain D (1953) The preparation of s-succinyl coenzyme A. J Am Chem Soc 75:2520
Solaro RJ, Pang DC, Briggs FN (1971) The purification of cardiac myofibrils with Triton X-100. Biochim Biophys Acta 245:259–262
Tanaka T, Hosaka K, Hoshimaru M, Numa S (1979) Purification and properties of long-chain acylcoenzyme-A synthetase from rat liver. Eur J Biochem 98:165–172
Tata JR (1964) Biological action of thyroid hormones at the cellular and molecular levels. In: Litwack G, Kritchevsky D (eds) Action of Hormones on Molecular Processes. John Wiley and Sons, New York, pp 58–131
Turakulov YaKh, Gagel'gans AI, Salakhova NS, Mirakhmedov AK, Gol'ber LM, Kandror VI, Gaidina GA (1975) Molecular mechanisms of action of thyroid hormones. In: Turakulov YaKh, Haigh B (eds) Thyroid Hormones. Plenum Publishing Corp, New York, pp 229–317
Valentine WN, Tanaka KR (1966) Pyruvate kinase: Clinical apects. In: Wood WA (ed) Methods of Enzymology. Academic Press, New York London, volume 9, pp 468–473
Weiss JL, Frederiksen JW, Weisfeldt ML (1976) Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin Invest 58:751–760
Wharton DC, Tzagoloff A (1967) Cytochrome oxidase from beef heart mitochondria. In: Estabrook RW, Pullman NE (eds) Methods of Enzymology. Academic Press, New York London, volume 10, pp 245–250
Yazaki Y, Raben MS (1975) Effect of the thyroid state on the enzymatic characteristics of cardiac myosin: A difference in behavior of rat and rabbit cardiac myosin. Circ Res 36:208–215
Young DL, Lynen F (1969) Enzymatic regulation of 3-Sn-phosphatidylcholine and triacylglycerol synthesis in states of altered lipid metabolism. J Biol Chem 244:377–383
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This study was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Science and Culture of the Japanese Government.
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Tanaka, T., Morita, H., Koide, H. et al. Biochemical and morphological study of cardiac hypertrophy. Effects of thyroxine on enzyme activities in the rat myocardium. Basic Res Cardiol 80, 165–174 (1985). https://doi.org/10.1007/BF01910464
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DOI: https://doi.org/10.1007/BF01910464