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. 1987 Jan;79(1):295–300. doi: 10.1172/JCI112798

Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue.

A C Bianco, J E Silva
PMCID: PMC424048  PMID: 3793928

Abstract

The effect of thyroxine (T4) and triiodothyronine (T3) on the expression of uncoupling protein (UCP) in rat brown adipose tissue (BAT) has been examined. Thyroidectomized rats have a threefold reduction in basal UCP levels. When exposed to cold, they become hypothermic and show a fivefold lower response of UCP than euthyroid controls. T3 augments the basal levels and the response of UCP and its mRNA to cold in a dose-dependent manner. However, to normalize the response of UCP, T3 has to be given in a dosage that produces systemic hyperthyroidism. Mere T3 replacement corrects the systemic hypothyroidism but not the hypothermia or the low levels of UCP. In contrast, replacement doses of T4 prevent the hypothermia and correct the UCP level. Both effects of T4 are blocked by preventing T4 to T3 conversion in BAT. Thus, the optimal UCP response to cold and protection against hypothermia require a high BAT T3 concentration, which is attained from euthyroid levels of T4 via the activation of the BAT T4 5'deiodinase during cold exposure, but not from euthyroid plasma T3 levels.

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Selected References

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

  1. BARKER S. B., KLITGAARD H. M. Metabolism of tissues excised from thyroxine-injected rats. Am J Physiol. 1952 Jul;170(1):81–86. doi: 10.1152/ajplegacy.1952.170.1.81. [DOI] [PubMed] [Google Scholar]
  2. Bachmann K., Arieli A., Burger A. G., Chinet A. E. Triiodothyronine (T3)-induced thermogenesis: altered T3-efficiency in tissues from fed, starved, and refed hypothyroid rats. Endocrinology. 1985 Sep;117(3):1084–1089. doi: 10.1210/endo-117-3-1084. [DOI] [PubMed] [Google Scholar]
  3. Cannon B., Nedergaard J. The biochemistry of an inefficient tissue: brown adipose tissue. Essays Biochem. 1985;20:110–164. [PubMed] [Google Scholar]
  4. Gardner R. S. A sensitive colorimetric assay for mitochondrial alpha-glycerophosphate dehydrogenase. Anal Biochem. 1974 May;59(1):272–276. doi: 10.1016/0003-2697(74)90033-5. [DOI] [PubMed] [Google Scholar]
  5. Himms-Hagen J. Brown adipose tissue metabolism and thermogenesis. Annu Rev Nutr. 1985;5:69–94. doi: 10.1146/annurev.nu.05.070185.000441. [DOI] [PubMed] [Google Scholar]
  6. Jacobsson A., Stadler U., Glotzer M. A., Kozak L. P. Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. J Biol Chem. 1985 Dec 25;260(30):16250–16254. [PubMed] [Google Scholar]
  7. Kates A. L., Himms-Hagen J. Defective cold-induced stimulation of thyroxine 5'-deiodinase in brown adipose tissue of the genetically obese (ob/ob) mouse. Biochem Biophys Res Commun. 1985 Jul 16;130(1):188–193. doi: 10.1016/0006-291x(85)90400-0. [DOI] [PubMed] [Google Scholar]
  8. Klingenberg M., Aquila H., Riccio P. Isolation of functional membrane proteins related to or identical with the ADP, ATP carrier of mitochondria. Methods Enzymol. 1979;56:407–414. doi: 10.1016/0076-6879(79)56039-x. [DOI] [PubMed] [Google Scholar]
  9. LEE Y. P., LARDY H. A. INFLUENCE OF THYROID HORMONES ON L-ALPHA-GLYCEROPHOSPHATE DEHYDROGENASES AND OTHER DEHYDROGENASES IN VARIOUS ORGANS OF THE RAT. J Biol Chem. 1965 Mar;240:1427–1436. [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Langone J. J. 125I-Labeled protein A: reactivity with IgG and use as a tracer in radioimmunoassay. Methods Enzymol. 1980;70(A):356–375. doi: 10.1016/s0076-6879(80)70064-2. [DOI] [PubMed] [Google Scholar]
  12. Larsen P. R., Frumess R. D. Comparison of the biological effects of thyroxine and triiodothyronine in the rat. Endocrinology. 1977 Apr;100(4):980–988. doi: 10.1210/endo-100-4-980. [DOI] [PubMed] [Google Scholar]
  13. Leonard J. L., Mellen S. A., Larsen P. R. Thyroxine 5'-deiodinase activity in brown adipose tissue. Endocrinology. 1983 Mar;112(3):1153–1155. doi: 10.1210/endo-112-3-1153. [DOI] [PubMed] [Google Scholar]
  14. Lin C. S., Klingenberg M. Isolation of the uncoupling protein from brown adipose tissue mitochondria. FEBS Lett. 1980 May 5;113(2):299–303. doi: 10.1016/0014-5793(80)80613-2. [DOI] [PubMed] [Google Scholar]
  15. Mory G., Ricquier D., Pesquiés P., Hémon P. Effects of hypothyroidism on the brown adipose tissue of adult rats: comparison with the effects of adaptation to cold. J Endocrinol. 1981 Dec;91(3):515–524. doi: 10.1677/joe.0.0910515. [DOI] [PubMed] [Google Scholar]
  16. Oppenheimer J. H., Coulombe P., Schwartz H. L., Gutfeld N. W. Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat. J Clin Invest. 1978 Apr;61(4):987–997. doi: 10.1172/JCI109024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
  18. Sajdel-Sulkowska E., Coughlin J. F., Marotta C. A. In vitro synthesis of polypeptides of moderately large size by poly(A)-containing messenger RNA from postmortem human brain and mouse brain. J Neurochem. 1983 Mar;40(3):670–680. doi: 10.1111/j.1471-4159.1983.tb08032.x. [DOI] [PubMed] [Google Scholar]
  19. Silva J. E., Larsen P. R. Adrenergic activation of triiodothyronine production in brown adipose tissue. Nature. 1983 Oct 20;305(5936):712–713. doi: 10.1038/305712a0. [DOI] [PubMed] [Google Scholar]
  20. Silva J. E., Larsen P. R. Interrelationships among thyroxine, growth hormone, and the sympathetic nervous system in the regulation of 5'-iodothyronine deiodinase in rat brown adipose tissue. J Clin Invest. 1986 Apr;77(4):1214–1223. doi: 10.1172/JCI112424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Silva J. E., Larsen P. R. Potential of brown adipose tissue type II thyroxine 5'-deiodinase as a local and systemic source of triiodothyronine in rats. J Clin Invest. 1985 Dec;76(6):2296–2305. doi: 10.1172/JCI112239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Silva J. E., Leonard J. L., Crantz F. R., Larsen P. R. Evidence for two tissue-specific pathways for in vivo thyroxine 5'-deiodination in the rat. J Clin Invest. 1982 May;69(5):1176–1184. doi: 10.1172/JCI110554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Triandafillou J., Gwilliam C., Himms-Hagen J. Role of thyroid hormone in cold-induced changes in rat brown adipose tissue mitochondria. Can J Biochem. 1982 May;60(5):530–537. doi: 10.1139/o82-065. [DOI] [PubMed] [Google Scholar]
  24. Wreschner D. H., Herzberg M. A new blotting medium for the simple isolation and identification of highly resolved messenger RNA. Nucleic Acids Res. 1984 Feb 10;12(3):1349–1359. doi: 10.1093/nar/12.3.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]

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