Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1970 May;49(5):1016–1024. doi: 10.1172/JCI106301

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

Jack H Oppenheimer 1, Harold L Schwartz 1, Harvey C Shapiro 1, Gerald Bernstein 1, Martin I Surks 1
PMCID: PMC535753  PMID: 5441537

Abstract

Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-125I and T3-131I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine.

Full text

PDF
1016

Selected References

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

  1. BEEKEN W. L., VOLWILER W., GOLDSWORTHY P. D., GARBY L. E., REYNOLDS W. E., STOGSDILL R., STEMLER R. S. Studies of I-131-albumin catabolism and distribution in normal young male adults. J Clin Invest. 1962 Jun;41:1312–1333. doi: 10.1172/JCI104594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bellabarba D., Peterson R. E., Sterling K. An improved method for chromatography of iodothyronines. J Clin Endocrinol Metab. 1968 Feb;28(2):305–307. doi: 10.1210/jcem-28-2-305. [DOI] [PubMed] [Google Scholar]
  3. Bernstein G., Artz S. A., Hasen J., Oppenheimer J. H. Hepatic accumulation of 125I-thyroxine in the rat: augmentation by phenobarbital and chlordane. Endocrinology. 1968 Feb;82(2):406–409. doi: 10.1210/endo-82-2-406. [DOI] [PubMed] [Google Scholar]
  4. Cavalieri R. R., Searle G. L. The kinetics of distribution between plasma and liver of 131-I-labeled L-thyroxine in man: observations of subjects with normal and decreased serum thyroxine-binding globulin. J Clin Invest. 1966 Jun;45(6):939–949. doi: 10.1172/JCI105409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GALTON V. A., INGBAR S. H. Observations on the effects and the metabolism of thyroid hormones in Necturus maculosus. Endocrinology. 1962 Sep;71:369–377. doi: 10.1210/endo-71-3-369. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Ingbar S. H., Braverman L. E., Dawber N. A., Lee G. Y. A new method for measuring the free thyroid hormone in human serum and an analysis of the factors that influence its concentration. J Clin Invest. 1965 Oct;44(10):1679–1689. doi: 10.1172/JCI105275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Irvine C. H. Qualitative and quantitative aspects of thyroxine metabolism in sheep. Endocrinology. 1969 Oct;85(4):662–673. doi: 10.1210/endo-85-4-662. [DOI] [PubMed] [Google Scholar]
  9. Nauman J. A., Nauman A., Werner S. C. Total and free triiodothyronine in human serum. J Clin Invest. 1967 Aug;46(8):1346–1355. doi: 10.1172/JCI105627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Oppenheimer J. H. Role of plasma proteins in the binding, distribution and metabolism of the thyroid hormones. N Engl J Med. 1968 May 23;278(21):1153–1162. doi: 10.1056/NEJM196805232782107. [DOI] [PubMed] [Google Scholar]
  13. Oppenheimer J. H., Surks M. I., Schwartz H. L. The metabolic significance of exchangeable cellular thyroxine. Recent Prog Horm Res. 1969;25:381–422. doi: 10.1016/b978-0-12-571125-8.50011-9. [DOI] [PubMed] [Google Scholar]
  14. ROBBINS J., RALL J. E. Proteins associated with the thyroid hormones. Physiol Rev. 1960 Jul;40:415–489. doi: 10.1152/physrev.1960.40.3.415. [DOI] [PubMed] [Google Scholar]
  15. SCHNEIDER W. C., HOGEBOOM G. H. Intracellular distribution of succinoxidase and cytochrome oxidase activities in normal mouse liver and in mouse hepatoma. J Natl Cancer Inst. 1950 Feb;10(4):969–975. [PubMed] [Google Scholar]
  16. STERLING K., LASHOF J. C., MAN E. B. Disappearance from serum of I131-labeled l-thyroxine and l-triiodothyronine in euthyroid subjects. J Clin Invest. 1954 Jul;33(7):1031–1035. doi: 10.1172/JCI102970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schussler G. C., Plager J. E. Effect of preliminary purification of 131-I-thyroxine on the determination of free thyroxine in serum. J Clin Endocrinol Metab. 1967 Feb;27(2):242–250. doi: 10.1210/jcem-27-2-242. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Surks M. I., Oppenheimer J. H. Formation of iodoprotein during the peripheral metabolism of 3,5,3'-triiodo-L-thyronine-125I in the euthyroid man and rat. J Clin Invest. 1969 Apr;48(4):685–695. doi: 10.1172/JCI106026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Surks M. I., Schwartz H. L., Oppenheimer J. H. Tissue iodoprotein formation during the peripheral metabolism of the thyroid hormones. J Clin Invest. 1969 Nov;48(11):2168–2175. doi: 10.1172/JCI106183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. TAIT J. F. REVIEW: THE USE OF ISOTOPIC STEROIDS FOR THE MEASUREMENT OF PRODUCTION RATES IN VIVO. J Clin Endocrinol Metab. 1963 Dec;23:1285–1297. doi: 10.1210/jcem-23-12-1285. [DOI] [PubMed] [Google Scholar]
  22. VANARSDEL P., Jr, HOGNESS J. R., WILLIAMS R. H., ELGEE N. Comparative distribution and fate of I131-labeled thyroxine and triiodothyronine. Endocrinology. 1954 Sep;55(3):332–343. doi: 10.1210/endo-55-3-332. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES