Abstract
Thyroxine, the major secretory product of the thyroid gland, is metabolized in the peripheral tissues by phenolic conjugation, deamination, decarboxylation, and a cascade of monodeiodinations. This brief review focuses on the deiodination reactions, which currently are under intensive investigation. One product, 3,5,3'-triiodothyronine (T3), is the major active form of the thyroid hormone, and about 80% of the T3 produced in the body is derived extrathyroidally. Furthermore, a greater fraction of the T3 found on nuclear receptors in pituitary and brain cells is derived intracellularly, as compared to liver and kidney cells. The latter tissues, on the other hand, appear to be the source of most of the circulating T3. Another deiodinase, acting on the nonphenolic ring of T4, gives rise to the hormonally inactive 3,3',5'-triiodothyronine ("reverse" T3 or rT3). A number of physiological and pathological events perturb the deiodination pathway, leading to a decrease in T3 neogenesis and reciprocal changes in the circulating level of T3 (which decreases) and rT3 (which increases). This so-called "low T3 syndrome" is also produced by a number of pharmacological agents. The biological effects resulting from these changes are incompletely understood, but they are potentially important in the body's adjustment to stress and as a site of action of toxic agents. In addition, they are of obvious importance clinically because of their influence on serum T3 and TSH levels, which are commonly used tests of thyroid function.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bastomsky C. H., Murthy P. V. Enchanced in vitro hepatic glucuronidation of thyroxine in rats following cutaneous application or ingestion of polychlorinated biphenyls. Can J Physiol Pharmacol. 1976 Feb;54(1):23–26. doi: 10.1139/y76-004. [DOI] [PubMed] [Google Scholar]
- Burger A., Dinichert D., Nicod P., Jenny M., Lemarchand-Béraud T., Vallotton M. B. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. J Clin Invest. 1976 Aug;58(2):255–259. doi: 10.1172/JCI108466. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bürgi H., Wimpfheimer C., Burger A., Zaunbauer W., Rösler H., Lemarchand-Béraud T. Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents. J Clin Endocrinol Metab. 1976 Dec;43(6):1203–1210. doi: 10.1210/jcem-43-6-1203. [DOI] [PubMed] [Google Scholar]
- Cavalieri R. R. Impaired peripheral conversion of thyroxine to triiodothyronine,. Annu Rev Med. 1977;28:57–65. doi: 10.1146/annurev.me.28.020177.000421. [DOI] [PubMed] [Google Scholar]
- Cheron R. G., Kaplan M. M., Larsen P. R. Divergent changes of thyroxine-5'-monodeiodination in rat pituitary and liver during maturation. Endocrinology. 1980 May;106(5):1405–1409. doi: 10.1210/endo-106-5-1405. [DOI] [PubMed] [Google Scholar]
- Chopra I. J., Williams D. E., Orgiazzi J., Solomon D. H. Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3'5-triiodothyronine (T3). J Clin Endocrinol Metab. 1975 Nov;41(5):911–920. doi: 10.1210/jcem-41-5-911. [DOI] [PubMed] [Google Scholar]
- Crantz F. R., Larsen P. R. Rapid thyroxine to 3,5,3'-triiodothyronine conversion and nuclear 3,5,3'-triiodothyronine binding in rat cerebral cortex and cerebellum. J Clin Invest. 1980 Apr;65(4):935–938. doi: 10.1172/JCI109749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dratman M. B., Crutchfield F. L. Synaptosomal [125I]triiodothyronine after intravenous [125I]thyroxine. Am J Physiol. 1978 Dec;235(6):E638–E647. doi: 10.1152/ajpendo.1978.235.6.E638. [DOI] [PubMed] [Google Scholar]
- Duick D. S., Warren D. W., Nicoloff J. T., Otis C. L., Croxson M. S. Effect of single dose dexamethasone on the concentration of serum triiodothyronine in man. J Clin Endocrinol Metab. 1974 Dec;39(6):1151–1154. doi: 10.1210/jcem-39-6-1151. [DOI] [PubMed] [Google Scholar]
- Fisher D. A., Dussault J. H., Sack J., Chopra I. J. Ontogenesis of hypothalamic--pituitary--thyroid function and metabolism in man, sheep, and rat. Recent Prog Horm Res. 1976;33:59–116. doi: 10.1016/b978-0-12-571133-3.50010-6. [DOI] [PubMed] [Google Scholar]
- Gavin L. A., Hammond M. E., Castle J. N., Cavalieri R. R. 3,3'-Diiodothyronine production, a major pathway of peripheral iodothyronine metabolism in man. J Clin Invest. 1978 May;61(5):1276–1285. doi: 10.1172/JCI109044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geffner D. L., Azukizawa M., Hershman J. M. Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man. J Clin Invest. 1975 Feb;55(2):224–229. doi: 10.1172/JCI107925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heyma P., Larkins R. G., Campbell D. G. Inhibition by propranolol of 3,5,3'-triiodothyronine formation from thyroxine in isolated rat renal tubules: an effect independent of beta-adrenergic blockade. Endocrinology. 1980 May;106(5):1437–1441. doi: 10.1210/endo-106-5-1437. [DOI] [PubMed] [Google Scholar]
- Kaplan M. M. Thyroxine 5'-monodeiodination in rat anterior pituitary homogenates. Endocrinology. 1980 Feb;106(2):567–576. doi: 10.1210/endo-106-2-567. [DOI] [PubMed] [Google Scholar]
- Kaplan M. M., Yaskoski K. A. Phenolic and tyrosyl ring deiodination of iodothyronines in rat brain homogenates. J Clin Invest. 1980 Sep;66(3):551–562. doi: 10.1172/JCI109887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leonard J. L., Rosenberg I. N. Thyroxine 5'-deiodinase activity of rat kidney: observations on activation by thiols and inhibition by propylthiouracil. Endocrinology. 1978 Dec;103(6):2137–2144. doi: 10.1210/endo-103-6-2137. [DOI] [PubMed] [Google Scholar]
- 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]
- Oppenheimer J. H., Schwartz H. L., Surks M. I. Determination of common parameters fo iodothyronine metabolism and distribution in man by noncompartmental analysis. J Clin Endocrinol Metab. 1975 Aug;41(2):319–324. doi: 10.1210/jcem-41-2-319. [DOI] [PubMed] [Google Scholar]
- Saberi M., Sterling F. H., Utiger R. D. Reduction in extrathyroidal triiodothyronine production by propylthiouracil in man. J Clin Invest. 1975 Feb;55(2):218–223. doi: 10.1172/JCI107924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silva J. E., Larsen P. R. Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute inhibition of thyroid-stimulating hormone release. J Clin Invest. 1978 May;61(5):1247–1259. doi: 10.1172/JCI109041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sorimachi K., Robbins J. Phenolic and nonphenolic ring deiodinations of iodothyronines in cultured hepatocarcinoma cell homogenate from monkey. Biochim Biophys Acta. 1979 Apr 3;583(4):443–453. doi: 10.1016/0304-4165(79)90061-8. [DOI] [PubMed] [Google Scholar]
- Spaulding S. W., Chopra I. J., Sherwin R. S., Lyall S. S. Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man. J Clin Endocrinol Metab. 1976 Jan;42(1):197–200. doi: 10.1210/jcem-42-1-197. [DOI] [PubMed] [Google Scholar]
- Suda A. K., Pittman C. S., Shimizu T., Chambers J. B., Jr The production and metabolism of 3,5,3'-triiodothyronine and 3,3',5-triiodothyronine in normal and fasting subjects. J Clin Endocrinol Metab. 1978 Dec;47(6):1311–1319. doi: 10.1210/jcem-47-6-1311. [DOI] [PubMed] [Google Scholar]
- Visser T. J., Fekkes D., Docter R., Hennemann G. Sequential deiodination of thyroxine in rat liver homogenate. Biochem J. 1978 Jul 15;174(1):221–229. doi: 10.1042/bj1740221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Visser T. J. Mechanism of inhibition of iodothyronine-5'-deiodinase by thioureylenes and sulfite. Biochim Biophys Acta. 1980 Feb 14;611(2):371–378. doi: 10.1016/0005-2744(80)90074-1. [DOI] [PubMed] [Google Scholar]
- Wu S. Y., Chopra I. J., Solomon D. H., Bennett L. R. Changes in circulating iodothyronines in euthyroid and hyperthyroid subjects given ipodate (Oragrafin), an agent for oral cholecystography. J Clin Endocrinol Metab. 1978 Apr;46(4):691–697. doi: 10.1210/jcem-46-4-691. [DOI] [PubMed] [Google Scholar]