• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Aug 1, 1989; 261(3): 945–950.
PMCID: PMC1138920

Rapid stimulation of hepatic oxygen consumption by 3,5-di-iodo-L-thyronine.


Tri-iodothyronine (T3) and thyroxine (T4) as well as 3,5-di-iodothyronine (T2) stimulated O2 consumption by isolated perfused livers from hypothyroid rats at a concentration as low as 1 pM by about 30% within 90 min. Application of T2 resulted in a faster stimulation than with application of T3 or T4. Inhibition of iodothyronine monodeiodinase by propylthiouracil, thereby blocking the degradation of T4 to T3 and of T3 to T2, demonstrated that only T2 is the active hormone for the rapid stimulation of hepatic O2 consumption: T3 and T4 lost all of their stimulative activity, whereas T2 was as potent as in the absence of propylthiouracil. Perfusion experiments with thyroid-hormone analogues confirmed the specificity of the T2 effect. The nucleus is unlikely to contribute to the rapid T2 effect, as can be deduced from perfusion experiments with cycloheximide and lack of induction of malic enzyme by T2. In conclusion, a new scheme of regulation of mitochondrial activity is proposed: T2 acts rapidly and directly via a mitochondrial pathway, whereas T3 exerts its long-term action indirectly by induction of specific enzymes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sterling K. Thyroid hormone action at the cell level (second of two parts). N Engl J Med. 1979 Jan 25;300(4):173–177. [PubMed]
  • Nelson BD, Mutvei A, Joste V. Regulation of biosynthesis of the rat liver inner mitochondrial membrane by thyroid hormone. Arch Biochem Biophys. 1984 Jan;228(1):41–48. [PubMed]
  • Müller MJ, Seitz HJ. Rapid and direct stimulation of hepatic gluconeogenesis by L-triiodothyronine (T3) in the isolated-perfused rat liver. Life Sci. 1980 Sep 8;27(10):827–835. [PubMed]
  • Dembri A. Effets métaboliques de la 3,5-diméthyl-3'-isopropyl-L-thyronine (DIMIT) et de la 3,5,3'-triiodo-L-thyronine (T3) dans le cerveau et le foie de rat hypothyroïdien. Analogies et différences. C R Seances Soc Biol Fil. 1987;181(4):344–354. [PubMed]
  • Sterling K, Brenner MA, Sakurada T. Rapid effect of triiodothyronine on the mitochondrial pathway in rat liver in vivo. Science. 1980 Oct 17;210(4467):340–342. [PubMed]
  • Mowbray J, Corrigall J. Short-term control of mitochondrial adenine nucleotide translocator by thyroid hormone. Eur J Biochem. 1984 Feb 15;139(1):95–99. [PubMed]
  • Crespo-Armas A, Mowbray J. The rapid alteration by tri-iodo-L-thyronine in vivo of both the ADP/O ratio and the apparent H+/O ratio in hypothyroid-rat liver mitochondria. Biochem J. 1987 Feb 1;241(3):657–661. [PMC free article] [PubMed]
  • Palacios-Romero R, Mowbray J. Evidence for the rapid direct control both in vivo and in vitro of the efficiency of oxidative phosphorylation by 3,5,3'-tri-iodo-L-thyronine in rats. Biochem J. 1979 Dec 15;184(3):527–538. [PMC free article] [PubMed]
  • Hafner RP, Brand MD. Hypothyroidism in rats does not lower mitochondrial ADP/O and H+/O ratios. Biochem J. 1988 Mar 1;250(2):477–484. [PMC free article] [PubMed]
  • Seitz HJ, Müller MJ, Soboll S. Rapid thyroid-hormone effect on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell. Biochem J. 1985 Apr 1;227(1):149–153. [PMC free article] [PubMed]
  • Sterling K. Direct thyroid hormone activation of mitochondria: the role of adenine nucleotide translocase. Endocrinology. 1986 Jul;119(1):292–295. [PubMed]
  • Höppner W, Horst C, Rasmussen UB, Seitz HJ. Adenine nucleotide translocase--a target of thyroid hormone action? Horm Metab Res Suppl. 1987;17:29–33. [PubMed]
  • Sterling K, Milch PO, Brenner MA, Lazarus JH. Thyroid hormone action: the mitochondrial pathway. Science. 1977 Sep 2;197(4307):996–999. [PubMed]
  • Engler D, Burger AG. The deiodination of the iodothyronines and of their derivatives in man. Endocr Rev. 1984 Spring;5(2):151–184. [PubMed]
  • Conversion of thyroxine into tri-iodothyronine by rat liver homogenate. Biochem J. 1975 Sep;150(3):489–493. [PMC free article] [PubMed]
  • Oppenheimer JH. Thyroid hormone action at the nuclear level. Ann Intern Med. 1985 Mar;102(3):374–384. [PubMed]
  • Gelehrter TD, Tomkins GM. Posttranscriptional control of tyrosine aminotransferase synthesis by insulin. Proc Natl Acad Sci U S A. 1970 Jun;66(2):390–397. [PMC free article] [PubMed]
  • Barker KL, Lee KL, Kenney FT. Turnover of tyrosine transaminase in cultured hepatoma cells after inhibition of protein synthesis. Biochem Biophys Res Commun. 1971 Jun 4;43(5):1132–1138. [PubMed]
  • Leeson PD, Ellis D, Emmett JC, Shah VP, Showell GA, Underwood AH. Thyroid hormone analogues. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart. J Med Chem. 1988 Jan;31(1):37–54. [PubMed]
  • Oppenheimer JH, Silva E, Schwartz HL, Surks MI. Stimulation of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme by L-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated. J Clin Invest. 1977 Mar;59(3):517–527. [PMC free article] [PubMed]
  • Koehrle J, Auf'mkolk M, Rokos H, Hesch RD, Cody V. Rat liver iodothyronine monodeiodinase. Evaluation of the iodothyronine ligand-binding site. J Biol Chem. 1986 Sep 5;261(25):11613–11622. [PubMed]
  • Segal J, Ingbar SH. In vivo stimulation of sugar uptake in rat thymocytes. An extranuclear action of 3,5,3'-triiodothyronine. J Clin Invest. 1985 Oct;76(4):1575–1580. [PMC free article] [PubMed]
  • Segal J. Biphasic stimulation of cellular calcium concentration by 3,5,3'-triiodothyronine in rat thymocytes. Biochemistry. 1988 Apr 5;27(7):2586–2590. [PubMed]
  • Hummerich H, Soboll S. Rapid stimulation of calcium uptake into rat liver by L-tri-iodothyronine. Biochem J. 1989 Mar 1;258(2):363–367. [PMC free article] [PubMed]
  • Davis FB, Cody V, Davis PJ, Borzynski LJ, Blas SD. Stimulation by thyroid hormone analogues of red blood cell Ca2+-ATPase activity in vitro. Correlations between hormone structure and biological activity in a human cell system. J Biol Chem. 1983 Oct 25;258(20):12373–12377. [PubMed]
  • Davidson AM, Halestrap AP. Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content. Biochem J. 1987 Sep 15;246(3):715–723. [PMC free article] [PubMed]
  • Haynes RC, Jr, Picking RA, Zaks WJ. Control of mitochondrial content of adenine nucleotides by submicromolar calcium concentrations and its relationship to hormonal effects. J Biol Chem. 1986 Dec 5;261(34):16121–16125. [PubMed]
  • Soboll S, Scholz R. Control of energy metabolism by glucagon and adrenaline in perfused rat liver. FEBS Lett. 1986 Sep 1;205(1):109–112. [PubMed]
  • Höppner W, Süssmuth W, O'Brien C, Seitz HJ. Cooperative effect of thyroid and glucocorticoid hormones on the induction of hepatic phosphoenolpyruvate carboxykinase in vivo and in cultured hepatocytes. Eur J Biochem. 1986 Sep 1;159(2):399–405. [PubMed]
  • Thomas WE, Crespo-Armas A, Mowbray J. The influence of nanomolar calcium ions and physiological levels of thyroid hormone on oxidative phosphorylation in rat liver mitochondria. A possible signal amplification control mechanism. Biochem J. 1987 Oct 15;247(2):315–320. [PMC free article] [PubMed]
  • Hashizume K, Kobayashi M, Miyamoto T, Yamauchi K. Dependence of the mitochondrial uptake of triiodothyronine (T3) in rat kidney on cytosolic T3-binding protein. Endocrinology. 1986 Sep;119(3):1063–1070. [PubMed]
  • Faber J, Kirkegaard C, Lumholtz IB, Siersbaek-Nielsen K, Friis T. Simultaneous measurement of 3,5-diiodothyronine and 3,5,3'-triiodothyronine turnover kinetics in euthyroid hyperthyroid, and hypothyroid subjects. J Clin Endocrinol Metab. 1982 Jul;55(1):8–12. [PubMed]
  • Nishikawa M, Inada M, Naito K, Ishii H, Tanaka K, Mashio Y, Imura H. Age-related changes of serum 3,3'-diiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine concentrations in man. J Clin Endocrinol Metab. 1981 Mar;52(3):517–522. [PubMed]
  • Gnoni GV, Geelen MJ, Bijleveld C, Quagliariello E, van den Bergh SG. Short-term stimulation of lipogenesis by triiodothyronine in maintenance cultures of rat hepatocytes. Biochem Biophys Res Commun. 1985 Apr 30;128(2):525–530. [PubMed]
  • Müller MJ, Seitz HJ. Dose dependent stimulation of hepatic oxygen consumption and alanine conversion to CO2 and glucose by 3,5,3'-triiodo-L-thyronine (T3) in the isolated perfused liver of hypothyroid rats. Life Sci. 1981 May 18;28(20):2243–2249. [PubMed]
  • Burger AG, O'Connell M, Scheidegger K, Woo R, Danforth E., Jr Monodeiodination of triiodothyronine and reverse triiodothyronine during low and high calorie diets. J Clin Endocrinol Metab. 1987 Nov;65(5):829–835. [PubMed]
  • Sims EA, Danforth E, Jr, Horton ES, Bray GA, Glennon JA, Salans LB. Endocrine and metabolic effects of experimental obesity in man. Recent Prog Horm Res. 1973;29:457–496. [PubMed]
  • Goldberg JR, Ehrmann B, Katzeff HL. Altered triiodothyronine metabolism in Zucker fatty rats. Endocrinology. 1988 Feb;122(2):689–693. [PubMed]
  • Underwood AH, Emmett JC, Ellis D, Flynn SB, Leeson PD, Benson GM, Novelli R, Pearce NJ, Shah VP. A thyromimetic that decreases plasma cholesterol levels without increasing cardiac activity. Nature. 1986 Dec 4;324(6096):425–429. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...