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. 1974 Apr;53(4):980–987. doi: 10.1172/JCI107664

Augmentation of the Peripheral Metabolism of l-Triiodothyronine and l-Thyroxine after Acclimation to Cold

MULTIFOCAL STIMULATION OF THE BINDING OF IODOTHYRONINES BY TISSUES

Alan Balsam 1, Lynn E Leppo 1
PMCID: PMC333082  PMID: 4815089

Abstract

Increased metabolism of thyroid hormones was observed in rats adapted to an ambient temperature of 4°C. The increased hormonal degradation was manifested in enhanced metabolic, urinary deiodinative, biliary, and fecal clearances of iodothyronines. Increased metabolic clearances were due to stimulation of cellular hormonal disposition, evidenced by elevated intrinsic cellular clearances. After adaptation, the concentration of protein-bound iodine in plasma was decreased, and the binding of the hormones by plasma proteins was increased. The enhanced rate of metabolism of iodothyronines was associated with stimulation of the binding of these hormones by diverse tissues, suggesting the participation of extrahepatic degradative foci in the increased hormonal deiodination observed in vivo. Increased hepatocellular binding and a significantly enlarged hepatic distribution space of thyroxine were noted. Hepatocellular binding of triiodothyronine was similarly augmented, and a smaller but significant increase in the hepatic space of this iodothyronine was detected. Analysis of the hepatic subcellular partition of iodothyronines 35 min after the intravenous administration of isotopically labeled thyroid hormones disclosed increased hormonal binding by the microsomal fraction in cold-adapted animals and an attendant increase in the microsomal protein concentration. Partial microsomal subfractionation in a discontinuous sucrose gradient indicated that the observed stimulation of microsomal hormonal binding was associated with proliferation of the smooth endoplasmic reticulum.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. COTTLE M., CARLSON L. D. Turnover of thyroid hormone in cold-exposed rats determined by radioactive iodine studies. Endocrinology. 1956 Jul;59(1):1–11. doi: 10.1210/endo-59-1-1. [DOI] [PubMed] [Google Scholar]
  2. COTTLE W. H. BILIARY AND FECAL CLEARANCE OF ENDOGENOUS THYROID HORMONE IN COLD-ACCLIMATED RATS. Am J Physiol. 1964 Nov;207:1063–1066. doi: 10.1152/ajplegacy.1964.207.5.1063. [DOI] [PubMed] [Google Scholar]
  3. ERSHOFF B. H., GOLUB O. J. Effects of prolonged exposure to cold on the serum protein-bound iodine of the rat. Arch Biochem. 1951 Jan;30(1):202–206. [PubMed] [Google Scholar]
  4. GREGERMAN R. I. Estimation of thyroxine secretion rate in the rat by the radioactive thyroxine turnover technique: influences of age, sex and exposure to cold. Endocrinology. 1963 Mar;72:382–392. doi: 10.1210/endo-72-3-382. [DOI] [PubMed] [Google Scholar]
  5. Galton V. A., Nisula B. C. Thyroxine metabolism and thyroid function in the cold-adapted rat. Endocrinology. 1969 Jul;85(1):79–86. doi: 10.1210/endo-85-1-79. [DOI] [PubMed] [Google Scholar]
  6. Gorman C. A., Flock E. V., Owen C. A., Jr, Paris J. Factors affecting exchange of thyroid hormones between liver and blood. Endocrinology. 1966 Aug;79(2):391–405. doi: 10.1210/endo-79-2-391. [DOI] [PubMed] [Google Scholar]
  7. HALE H. B., MEFFERD R. B., Jr, VAWTER G., FOERSTER G. E., CRISCUOLO D. Influence of long-term exposure to adverse environments on organ weights and histology. Am J Physiol. 1959 Mar;196(3):520–524. doi: 10.1152/ajplegacy.1959.196.3.520. [DOI] [PubMed] [Google Scholar]
  8. HENINGER R. W., LARSON F. C., ALBRIGHT E. C. IODINE-CONTAINING COMPOUNDS OF EXTRATHYROIDAL TISSUES. J Clin Invest. 1963 Nov;42:1761–1768. doi: 10.1172/JCI104861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hasen J., Bernstein G., Volpert E., Oppenheimer J. H. Analysis of the rapid interchange of thyroxine between plasma and liver and plasma and kidney in the intact rat. Endocrinology. 1968 Jan;82(1):37–46. doi: 10.1210/endo-82-1-37. [DOI] [PubMed] [Google Scholar]
  10. Hillier A. P. Thyroxine deiodination during cold exposure in the rat. J Physiol. 1968 Jul;197(1):135–147. doi: 10.1113/jphysiol.1968.sp008551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Héroux O., Petrovic V. M. Effect of high- and low-bulk diets on the thyroxine turnover rate in rats with acute and chronic exposure to different temperatures. Can J Physiol Pharmacol. 1969 Dec;47(12):963–968. doi: 10.1139/y69-157. [DOI] [PubMed] [Google Scholar]
  12. INTOCCIA A., VAN MIDDLESWORTH L. Thyroxine excretion increase by cold exposure. Endocrinology. 1959 Mar;64(3):462–464. doi: 10.1210/endo-64-3-462. [DOI] [PubMed] [Google Scholar]
  13. ISSELBACHER K. J. Enzymatic mechanisms of hormone metabolism. II. Mechanism of hormonal glucuronide formation. Recent Prog Horm Res. 1956;12:134-46; discussion, 146-51. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Nakagawa S., Ruegamer W. R. Properties of a rat tissue iodothyronine deiodinase and its natural inhibitor. Biochemistry. 1967 May;6(5):1249–1261. doi: 10.1021/bi00857a005. [DOI] [PubMed] [Google Scholar]
  16. OPPENHEIMER J. H., SQUEF R., SURKS M. I., HAUER H. BINDING OF THYROXINE BY SERUM PROTEINS EVALUATED BY EQUILIBRUM DIALYSIS AND ELECTROPHORETIC TECHNIQUES. ALTERATIONS IN NONTHYROIDAL ILLNESS. J Clin Invest. 1963 Nov;42:1769–1782. doi: 10.1172/JCI104862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Oppenheimer J. H., Bernstein G., Surks M. I. Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital. J Clin Invest. 1968 Jun;47(6):1399–1406. doi: 10.1172/JCI105831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oppenheimer J. H., Schwartz H. L., Shapiro H. C., Bernstein G., Surks M. I. Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3'-L-triiodothyronine and L-thyroxine. J Clin Invest. 1970 May;49(5):1016–1024. doi: 10.1172/JCI106301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schwartz H. L., Bernstein G., Oppenheimer J. H. Effect of phenobarbital administration on the subcellular distribution of 125-I-thyroxine in rat liver: mportance of microsomal binding. Endocrinology. 1969 Feb;84(2):270–276. doi: 10.1210/endo-84-2-270. [DOI] [PubMed] [Google Scholar]
  20. Schwartz H. L., Kozyreff V., Surks M. I., Oppenheimer J. H. Increased deiodination of L-thyroxine and L-triiodothyronine by liver microsomes from rats treated with phenobarbital. Nature. 1969 Mar 29;221(5187):1262–1263. doi: 10.1038/2211262a0. [DOI] [PubMed] [Google Scholar]
  21. TATA J. R., ERNSTER L., SURANYI E. M. Interaction between thyroid hormones and cellular constituent. II. Intracellular distribution and the cell-sap effect. Biochim Biophys Acta. 1962 Jul 16;60:480–491. doi: 10.1016/0006-3002(62)90867-3. [DOI] [PubMed] [Google Scholar]
  22. WYNN J., GIBBS R., ROYSTER B. Thyroxine degradation. I. Study of optimal reaction conditions of a rat liver thyroxine-degrading system. J Biol Chem. 1962 Jun;237:1892–1897. [PubMed] [Google Scholar]

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