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Thyroid hormone action on intermediary metabolism

Part I: Respiration, thermogenesis and carbohydrate metabolism

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Summary

The effect of thyroid hormones on mitochondrial respiration are summarized: T3 directly stimulates mitochondrial respiration and the synthesis of adenosine 5′-triphosphate (ATP). Cytosolic ATP availability is increased by a thyroid hormone-induced increase in adenine nucleotide translocation across the mitochondrial membrane; the steady state ATP concentration and the cytosolic ATP/adenosine 5′-diphosphate (ADP) ratio is even decreased in hyperthyroid tissues because of the simultaneous stimulation of the synthesis and consumption of ATP. With regard to the thyroid hormone-induced energy wasting processes, heart work, intra- and interorgan futile cycling and Na+/K+-ATPase are involved to varying degrees. As a consequence of the thyroid hormone-induced hydrolysis of ATP, thermogenesis is increased in hyper- and decreased in hypothyroidism. Despite an increased rate of glucose utilization, clinical and experimental hyperthyroidism is often characterized by an abnormal oral glucose tolerance test. This finding is due to the thyroid hormone-induced increase in intestinal glucose absorption as well as the still enhanced endogenous glucose production in the liver. Hypothyroid patients show a reduced glucose tolerance test because of a decrease in intestinal glucose absorption and a sometimes reduced glucose turnover. The thyroid hormone-induced alterations in glucose metabolism are most probably not due to alterations in serum insulin levels and/or to a peripheral insulin resistance at the receptor level.

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References

  1. Acheson KJ, Burger AG (1980) A study of the relationship between thermogenesis and thyroid hormones. J Clin Endocrin Metab 51:84–89

    Google Scholar 

  2. Andersen WT (1933) Studies on blood sugar, and glucosurie in exophthalmic goitre. Acta Med Scand 54:1–206

    Google Scholar 

  3. Babior JM, Creagan S, Ingbar SH et al (1973) Stimulation of mitochondrial adenosine diphosphate uptake by thyroid hormones. Proc Nat Acad Sci USA 70:98–102

    Google Scholar 

  4. Baldwin KN, Hooker AM, Herrick RE et al. (1980) Respiratory capacity and glycogen depletion in thyroid deficient muscle. J Appl Physiol 49:102–106

    Google Scholar 

  5. Baquer NZ, Cascales M, McLean P et al (1976) Effects of thyroid hormones deficiency on the distribution of hepatic metabolites and control of pathways of carbohydrate metabolism in liver and adipose tissue of the rat. Eur J Biochem 68:403–413

    Google Scholar 

  6. Berry MN, Werner HV, Kun E (1974) Regulatory function of intercompartmental metabolite and reducing—equivalent translocation in hepatic gluconeogenesis. Role of thyroid hormone. In: Lundquist F, Tygstrup N (eds) Regulation of hepatic metabolism. Academic Press, New York, pp 501–519

    Google Scholar 

  7. Bestermann HS, Sarson DL, Hsu G et al (1979) GUT-hormones in thyrotoxicosis and anorexia nervosa. J Endocrinol 81:143P

    Google Scholar 

  8. Biron R, Burger A, Chinet A et al (1979) Thyroid hormones and the energetics of active sodium-potassium transport in mammalian skeletal muscles. J Physiol (Lond) 297:47–60

    Google Scholar 

  9. Blum JW, Gingins M, Vitins P et al (1980) Thyroid hormone levels related to energy and nitrogen balance during weight loss and regain in adult sheep. Acta Endocrinol 93:440–442

    Google Scholar 

  10. Burger AG, Hughes JN, Saville E (1981) Starvation and thyroid function: effects on thermogenesis and serum thyrotropin. Life Sci 28:1737–1744

    Google Scholar 

  11. Burns AH, Reddy WJ (1975) Direct effect of thyroid hormones on glucose oxidation by isolated rat cardiac myocytes. J Mol Cell Cardiol 7:553–561

    Google Scholar 

  12. Chopra IJ (1981) Triiodothyronines in health and disease. Springer Verlag, Berlin

    Google Scholar 

  13. Clark DG, Brinkman M, Filsell OH et al (1982) No major thermogenic role for (Na++K+)-dependent adenosine triphosphatase apparent in hepatocytes from hyperthyroid rats. Biochem J 202:661–665

    Google Scholar 

  14. Colton DG, Mehlman MA, Ruegamer WR (1972) Effect of thyroxine and 5,5-diphenyl-2-thiohydantoin on enzyme activities of rat liver and kidney. Endocrinology 90:1521–1528

    Google Scholar 

  15. Czech MP, Malbon CC, Kerman K et al (1980) Effect of thryoid status on insulin action in rat adipocytes and skeletal muscle. J Clin Invest 66:574–582

    Google Scholar 

  16. Dahlberg PA, Karlsson FA, Lundqvist G (1981) High serum gastrin levels in thyrotoxic patients. Clin Endocrinol 14:125–131

    Google Scholar 

  17. Danforth E, Horton ES, O'Connell M et al (1979) Dietary-induced alterations in thyroid hormone metabolism during overnutrition. J Clin Invest 64:1336–1347

    Google Scholar 

  18. Danforth E, Burger AG (1981) Hormonal control of thermogenesis. In: Cioffi LA, James WPT, v Itallie TB (eds) The body weight regulatory system: normal and disturbed mechanisms. Raven Press, New York, pp 107–114

    Google Scholar 

  19. McDaniel HG, Pittman CS, Oh SJ et al (1977) Carbohydrate metabolism in hypothyroid myopathy. Metabolism 26:867–873

    Google Scholar 

  20. Fain JN (1980) Hormonal regulation of lipid mobilization from adipose tissue. In Litwack G (ed) Biochemical actions of hormones, vol VII. Academic Press, New York, pp 119–204

    Google Scholar 

  21. Fain JN (1981) Catecholamine-thyroid hormone interactions in liver and adipose tissue. Life Sci 28:1745–1754

    Google Scholar 

  22. Goglia F, Torresani J, Bugli P et al (1981) In vitro binding of triiodothyronine to rat liver mitochondria. Pflügers Arch 390:120–124

    Google Scholar 

  23. De Groot LJ (1979) Thyroid Hormone Action. In: De Groot LJ, Calull GF, Odell WD et al (eds) Endocrinology. Grune & Stratton, New York, pp 357–363

    Google Scholar 

  24. Gross NJ (1971) Control of mitochondrial turnover under the influence of thyroid hormone. J Cell Biol 48:29–37

    Google Scholar 

  25. Gumaa KA, Hothersall JS, Greenbaum AL et al (1977) Thyroid hormone control of cyclic nucleotide phosphodiesterases and the regulation of the sensitivity of the liver to hormones. FEBS Let 80:45–48

    Google Scholar 

  26. Hanson RW, Lindsay RH, Barker SB (1961) Effect of thyroxine on metabolism of glucose and amino acids by rat kidney cortex. Endocrinology 69:883–895

    Google Scholar 

  27. van Hardeveld C, Kassenaar AAH (1977) Influence of experimental hyperthyroidism on skeletal muscle metabolism in the rat. Acta Endocrinol 85:71–83

    Google Scholar 

  28. van Hardeveld C, Kassenaar AAH (1978) Effects of experimental hypothyroidism on skeletal muscle metabolism in the rat. Acta Endocrinol 87:114–124

    Google Scholar 

  29. Hensgens LAM, Nieuwenhuis BJWM, van der Meer R et al (1980) The role of hydrogen translocation shuttles during ethanol oxydation in hepatocytes from euthyroid and hyperthyroid rats. Eur J Biochem 108:39–45

    Google Scholar 

  30. Himms-Hagen J (1976) Cellular thermogenesis. Ann Rev Physiol 38:315–351

    Google Scholar 

  31. Hoch FC (1977) Adenine nucleotide translocation in mitochondria of hypothyroid rats. Arch Biochem Biophys 178:535–545

    Google Scholar 

  32. Hogan S, Himms-Hagen J (1981) Abnormal brown adipose tissue in genetically obese mice (ob/ob): effect of thyroxine. Am J Physiol 241:E436-E443

    Google Scholar 

  33. Holdsworth CD, Besser HM (1968) Influence of gastric emptying-rate and of insulin response on oral glucose tolerance in thyroid disease. Lancet I:700–702

    Google Scholar 

  34. Houssay BA (1944) Thyroid and metathyroid diabetes. Endocrinology 35:158–172

    Google Scholar 

  35. Huang MT, Lardy HA (1981) Effects of thyroid states on the cori cycle, glucose-alanine cycle and futile cycling of glucose metabolism in the rat. Arch Biochem Biophys 209:41–51

    Google Scholar 

  36. Ingbar SH, Woeber KA (1981) The Thyroid Gland. In Williams RH (ed) Textbook of Endocrinology, 6th edition. WB Saunders Philadelphia, pp 117–247

  37. Kaminski T (1980) Stimulation of gluconeogenesis by thyroid hormones in isolated rat hepatocytes. Acta Endocrinol 94 [Suppl] (Kbh) 234:15–16

    Google Scholar 

  38. Laker ME, Mayes PA (1981) Effect of hyperthyroidism and hypothyroidism on lipid and carbohydrate metabolism of the perfused rat liver. Biochem J 196:247–255

    Google Scholar 

  39. Lenzen S (1978) Dose-response studies on the inhibitory effect of thyroid hormones on insulin secretion in the rat. Metabolism 27:81–88

    Google Scholar 

  40. Levy LJ, Adesman SJ, Spergel G (1970) Studies on the carbohydrate and lipid metabolism in thyroid disease effects of glucagon. J Clin Endocrinol Metab 30:372–376

    Google Scholar 

  41. Loeb JN (1979) Metabolic Changes. In: Ingbar SH & Werner SC (eds) The Thyroid. Harper & Row, New York, pp 705–712 and pp 872–877

    Google Scholar 

  42. Malbon CC, Lo Presti JJ (1981) Hyperthyroidism impairs the activation of glycogen phosphorylase by epinephrine in rat hepatocytes. J Biol Chem 256:12199–12204

    Google Scholar 

  43. Malbon CC, Greenberg ML (1982) 3,3′,5-triiodothyronine administration in vivo modulates the hormone-sensitive adenylate cyclase system of rat hepatocytes. J Clin Invest 69:414–426

    Google Scholar 

  44. Marecek RC, Feldman JM (1973) Steady state glucose dynamics in hyperthyroid rabbits. Res Commun Chem Pathol Pharmacol 5:493–504

    Google Scholar 

  45. Maréchaud R, Rambaud JC, Matuchansky C (1980) Intestinal manifestations of thyroid diseases: current clinical and pathophysiological aspects. Gastroenterol Clin Biol 4:899–910

    Google Scholar 

  46. Mirsky A, Broh-Kahn RH (1963) The effect of experimental hyperthyroidism on carbohydrate metabolism. Am J Physiol 117:6–12

    Google Scholar 

  47. Morgan DW, Shaheen O, Keyes WG et al (1982) Modulation by the thyroid status of hepatic low km phosphodiesterase. Endocrinology 110:260–264

    Google Scholar 

  48. Müller MJ, Seitz HJ (1980) Rapid and direct stimulation of hepatic gluconeogenesis by L-triiodothyronine in the isolated perfused rat liver. Life Sci 27:827–835

    Google Scholar 

  49. Müller MJ, Seitz HJ (1980) In vivo glucose turnover in hypo-and hyperthyroid starved rats. Pflügers Arch 386:47–52

    Google Scholar 

  50. Müller MJ, Seitz HJ (1981) Starvation induced changes of hepatic glucose metabolism in hypo- and hyperthyroid rats in vivo. J Nutr 111:1370–1379

    Google Scholar 

  51. Müller MJ, Seitz HJ (1981) Dose dependent stimulation of hepatic oxygen consumption and alanine conversion to CO2 and glucose by L-3,5,3′-triiodothyronine in the isolated perfused liver of hypothyroid rats. Life Sci 28:2243–2249

    Google Scholar 

  52. Müller MJ, Paschen U, Seitz HJ (1983) Thyroid hormone regulation of glucose homoeostasis in the miniature pig. Endocrinology 112:2025–2031

    Google Scholar 

  53. Müller MJ, Seitz HJ (1983) Interaction of thyroid hormones and cyclic AMP in stimulation of hepatic gluconeogenesis. Biochim. Biophys. Acta 756:360–368

    Google Scholar 

  54. Nakashima T, Traurog A, Krulich L (1981) Serum thyroxine, triiodothyronine and TSH levels in iodine-deficient and iodine sufficient rats before and after exposure to cold. Proc Soc Exp Biol Med 167:45–50

    Google Scholar 

  55. Nishiki K, Erecinska M, Wilson DF et al (1978) Evaluation of oxidative phosphorylation in hearts from euthyroid, hypothyroid and hyperthyroid rats. Am J Physiol 235:C212-C219

    Google Scholar 

  56. Nunez J, Correze C (1981) Interdependent effects of thyroid hormones and cAMP on lipolysis and lipogenesis in the fat cell. In: Dumont JE, Greengard P (eds) Adv Cyclic Nucleotide Res, vol 14. Raven Press, New York, pp 539–555

    Google Scholar 

  57. Okajima F, Ui M (1979) Metabolism of glucose in hyper- and hypothyroid rats in vivo. Biochem J 182:585–592

    Google Scholar 

  58. Okajima F, Ui M (1979) Metabolism of glucose in hypo- and hyperthyroid rats in vivo. Biochem J 182:565–575

    Google Scholar 

  59. Okajima F, Ui M (1979) Metabolism of glucose in hyper- and hypothyroid rats in vivo. Biochem J 182:577–584

    Google Scholar 

  60. Oppenheimer JH (1979) Thyroid hormone action at the cellular level. Science 203:971–979

    Google Scholar 

  61. Palacios-Romero R, Mowbray J (1979) Evidence for the rapid direct control both in vivo and in vitro of the efficiency of oxidative phosphorylation by 3,5,3′-triiodothyronine in rats. Biochem J 184:527–538

    Google Scholar 

  62. Perez G, Ungaro B, Covelli A et al (1980) Altered glucoregulatory response to physiological infusions of epinephrine and glucagon in hyperthyroidism. J Clin Endocrinol Metab 51:972–977

    Google Scholar 

  63. Preiksaitis HG, Kunos G (1979) Adrenoreceptor-mediated activation of liver glycogen phosphorylase: Effects of thyroid state. Life Sci 24:35–42

    Google Scholar 

  64. Rabinowitz JL, Myerson RM (1967) The effects of triiodothyronine on some metabolic parameters of obese individuals. Metabolism 16:68–75

    Google Scholar 

  65. Rognstad R (1977) Futile hydrogen cycling in liver cells from triiodothyronine treated rats. Biochem Biophys Res Commun 78:881–888

    Google Scholar 

  66. Roques M, Tirard A, De Groot LJ (1977) Liver protein kinase activity and triiodothyronine. Endocrinology 100:967–973

    Google Scholar 

  67. Saunders J, Hall SEH, Sönksen PH (1980) Glucose and free fatty acid turnover in thyrotoxicosis and hypothyroidism before and after treatment. Clin Endocrinol 13:33–44

    Google Scholar 

  68. Segal J, Ingbar SH (1980) Stimulation of 2-Deoxy-D-glucose uptake in rat thymocytes in vitro by physiological concentrations of triiodothyronine, insulin or epinephrine. Endocrinology 107:1354–1358

    Google Scholar 

  69. Segal J, Ingbar SH (1981) Studies of the mechanism by which 3,5,3′-triiodothyronine stimulates 2-deoxyglucose up-take in rat thymocytes in vitro. J Clin Invest 68:103–110

    Google Scholar 

  70. Sestoft L (1980) Metabolic aspects of the calorigenic action of thyroid hormones in mammals. Clin Endocrinol 13:489–506

    Google Scholar 

  71. Sestoft L, Heding LG (1981) Hypersecretion of proinsulin in thyrotoxicosis. Diabetologia 21:103–107

    Google Scholar 

  72. Shah JH, Motto GS, Papagiannes E et al (1975) Insulin metabolism in hypothyroidism. Diabetes 24:922–925

    Google Scholar 

  73. Shames DM, Berman M, Segal S (1971) Effects of thyroid disease on glucose oxidative metabolism in man. A compartmental model analysis. J Clin Invest 50:627–641

    Google Scholar 

  74. Shears SB (1980) The thyroid gland and the liver mitochondrial protonic electrochemical potential difference: a novel hormone action? J Theor Biol 82:1–13

    Google Scholar 

  75. Sibrowski W, Müller MJ, Seitz HJ (1981) Effect of different thyroid states on rat liver glucokinase synthesis and degradation in vivo. J Biol Chem 256:9490–9494

    Google Scholar 

  76. Sibrowski W, Müller MJ, Thomsen A et al (1982) Renal Phosphoenolpyruvate carbooxykinase turnover in hypo- and hyperthyroid rat in vivo. Biochim Biophys Acta 717:20–25

    Google Scholar 

  77. Sibrowski W, Müller MJ, Seitz HJ (1982) Rate of synthesis and degradation of rat liver phosphoenolpyruvate carboxykinase in the different thyroid states. Arch Biochem Biophys 213:327–333

    Google Scholar 

  78. Singh SP, Snyder AK (1978) Effect of thyrotoxicosis on gluconeogenesis from alanine in the perfused rat liver. Endocrinology 102:182–187

    Google Scholar 

  79. Smith TJ, Edelman IS (1979) The role of sodium transport in thyroid thermogenesis. Fed Proc 38:2150–2153

    Google Scholar 

  80. Somjen D, Ismail-Beigi F, Edelman IS (1981) Nuclear binding of T3 and effect on QO2, Na-K-ATPase and α-GPDH in liver and kidney. Am J Physiol 240:E146-E154

    Google Scholar 

  81. Sperling MA, Ganguli S, Voina S et al (1980) Modulation by thyroid status of the glucagon receptor-adenyl cyclase system in rat liver plasma membranes. Endocrinology 107:684–690

    Google Scholar 

  82. Sterling K, Brenner MA, Sakurada T: Rapid effect of triiodothyronine on the mitochondrial pathway in rat liver in vivo. Science 210:340–342

  83. Sterling K (1979) Thyroid hormone action at the cell level. N Engl J Med 300:117–123 and 173–177

    Google Scholar 

  84. Tata JR, Ernster L, Lindberg O et al (1963) The action of thyroid hormones at the cell level. Biochem J 86:408–428

    Google Scholar 

  85. Tata JR (1975) How specific are nuclear “receptors” for thyroid hormones. Nature 257:18–23

    Google Scholar 

  86. Wahren J, Wennlund A, Nilsson LH et al (1981) Influence of hyperthyroidism on splanchnic exchange of glucose and gluconeogenic precursors. J Clin Invest 67:1056–1063

    Google Scholar 

  87. Winder WJ (1979) Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria. Am J Physiol 236:C132-C138

    Google Scholar 

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  1. Institut für Physiologische Chemie, Universitäts-Krankenhaus Eppendorf, Germany

    M. J. Müller & H. J. Seitz

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  1. M. J. Müller
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Thyroid hormones are defined as 3,5,3′,5′-tetraiodothyronine (thyroxine-T4) and its deiodinated or non-deiodinated metabolic products providing thyroimimetic activity, mainly 3,5,3′-triiodothyronine (T3) [12]

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Müller, M.J., Seitz, H.J. Thyroid hormone action on intermediary metabolism. Klin Wochenschr 62, 11–18 (1984). https://doi.org/10.1007/BF01725187

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