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Endocrine
Published in: Endocrine 1/2019

01-10-2019 | Original Article

The isolation of thyroxine (T4), the discovery of 3,5,3’-triiodothyronine (T3), and the identification of the deiodinases that generate T3 from T4: An historical review

Authors: John C. Morris, Valerie Anne Galton

Published in: Endocrine | Issue 1/2019

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Excerpt

The thyroid gland was first described in the 17th century. However, the concept that this organ might have a functional role in the body was not recognized until the 19th century, when cretinism and myxedema were associated with thyroid atrophy, surgical thyroidectomy was found to result in symptoms comparable to those seen in patients with myxedema [1] and Murray demonstrated that myxedema could be treated successfully with daily injections of sheep thyroid extract [2]. These findings suggested that the thyroid secreted an active principle(s) essential for the prevention of myxedema, and in 1914 Kendall succeeded in isolating from the thyroid the compound now recognized as thyroxine (T4). …
Literature
1.
J. Lindholm, P. Laurberg, Hypothyroidism and thyroid substitution: historical aspects. J. Thyroid Res. 2011, 1–10 (2011)CrossRef
2.
G.R. Murray, Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of sheep. Brit. Med. J. 2, 786–797 (1891)CrossRef
3.
E. C. Kendall, Cortisone (Charles Scribner’s Sons, New York, 1971).
4.
E. Baumann, [Ueber das normale Vorkommen von Jod im Thierkorper]. Z. Physiol. Chem. 21, 319–330 (1896).
5.
H. Clapesattle, The Doctors Mayo (Mayo Clinic, Rochester, Minnesota, 1969).
6.
T Rooke. The Quest for Cortisone (Michigan State University Press, Lansing Michigan, (2012).
7.
E.C. Kendall, The isolation in crystalline form of the compound containing iodine which occurs in the thyroid gland. J. Am. Med. Assoc. 64, 2042–2043 (1915)CrossRef
8.
9.
10.
J.H. Means, Therapeutics of the thyroid. J. Am. Med. Assoc. 105, 24–28 (1935)CrossRef
11.
C.R. Harington, Bichemical basis of thyroid function. Lancet 225, 1261–1267 (1935)CrossRef
12.
C.R. Harington, Croonian lecture: thyroxine: its biosynthesis and its immunochemistry. Proc. R. Soc. Lond. Ser. B 132, 223–238 (1944)CrossRef
13.
A. Taurog, I.L. Chaikoff, The nature of the circulating thyroid hormone. J. Biol. Chem. 176, 639–656 (1948)PubMed
14.
15.
J. Gross et al. Presence of iodinated amino acids in unhydrolyzed thyroid and plasma. Science 111, 605–608 (1950)CrossRefPubMed
16.
17.
S.C. Kaufman, Thyroid hormone use: trends in the United States from 1960 through 1988. Thyroid 1, 285–291 (1991)CrossRefPubMed
18.
J. Gross, R. Pitt-Rivers, The identification of 3,5,3’L-triiodothyronine in human plasma. Lancet 259, 439–441 (1952)CrossRef
19.
20.
J. Roche, S. Lissitsky, R. Michel, Sur la presence de triiodothyronine dans la thyroglobuline. C. R. Acad. Sci. 234, 1228–1230 (1952)
21.
J. Gross, R. Pitt-Rivers, W.R. Trotter, Effect of 3,5,3’-L-triiodothyronine in myxoedema. Lancet 259, 1044–1045 (1952)CrossRef
22.
J. Gross, R. Pitt-Rivers, Physiological activity of 3:5:3’-L-Triiodothyronine. Lancet 259, 593–594 (1952)CrossRef
23.
24.
R. Pitt-Rivers, J.B. Stanbury, B. Rapp, Conversion of thyroxine to 3,5,3’-triiodothyronine in vivo. J. Clin. Endocrinol. Metab. 15, 616–620 (1955)CrossRefPubMed
25.
W.E. Lassiter, J.B. Stanbury, In vivo conversion of thyroxine to 3,5,3’ triiodothyronine. J. Clin. Endocrinol. Metab. 18, 903–906 (1958)CrossRefPubMed
26.
E.C. Albright, F.C. Larson, R.H. Tust, In vitro conversion of thyroxine to triiodothyronine by kidney slices. Proc. Soc. Expt. Biol. Med. 86, 137–140 (1954)CrossRef
27.
28.
29.
L.E. Braverman, S.H. Ingbar, K. Sterling, Conversion of thyroxine to triiodothyronine in athyreotic human subjects. J. Clin. Invest. 49, 855–864 (1970)CrossRefPubMedPubMedCentral
30.
K. Sterling, M.A. Brenner, E.S. Newman, Conversion of thyroxine to triiodothyronine in normal human subjects. Science 169, 1099–1100 (1970)CrossRefPubMed
31.
J.H. Oppenheimer et al. Specific nuclear triidothyronine binding sites in rat liver and kidney. J. Clin. Endocrinol. Metab. 35, 330–333 (1972)CrossRefPubMed
32.
A.R. Schadlow et al. Specific triiodothyronine binding sites in the anterior pituitary of the rat. Science 176, 1252–1254 (1972)CrossRefPubMed
33.
H.H. Samuels, J.S. Tsai, Thyroid hormone action in cell culture: demonstration of nuclear receptors in intact cells and isolated nuclei. Proc. Natl Acad. Sci. USA 12, 3488–3494 (1973)CrossRef
34.
J.H. Oppenheimer et al. Limited binding capacity sites for L-triiodothyronine in rat liver nuclei. Nuclear-cytoplasmic interrelation, binding constants, and cross- reactivity with L-thyroxine. J. Clin. Invest. 53, 768–677 (1974)CrossRefPubMedPubMedCentral
35.
M.I. Surks, J.H. Oppenheimer, Concentration of L-thyroxine and L-triiodothyronine specifically bound to nuclear receptors in rat liver and kidney. J. Clin. Invest. 60, 555–562 (1977)CrossRefPubMedPubMedCentral
36.
T.J. Visser et al. Subcellular localization of a rat liver enzyme converting thyroxine into tri- iodothyronine and possible involvement of essential thiol groups. Biochem. J. 157, 479–482 (1976)CrossRefPubMedPubMedCentral
37.
J.E. Silva, P.R. Larsen, Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine and 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. 61, 1247–1259 (1978)CrossRefPubMedPubMedCentral
38.
P.R. Larsen et al. Inhibition of intrapituitary thyroxine to 3.5.3’-triiodothyronine conversion prevents the acute suppression of thyrotropin release by thyroxine in hypothyroid rats. J. Clin. Invest. 64, 117–128 (1979)CrossRefPubMedPubMedCentral
39.
T.J. Visser et al. Evidence for two pathways of iodothyronine 5’-deiodination in rat pituitary that differ in kinetics, propylthiouracil sensitivity, and response to hypothyroidism. J. Clin. Invest. 71, 992–1002 (1983)CrossRefPubMedPubMedCentral
40.
T.J. Visser. et al. Kinetic evidence suggesting two mechanisms for iodothyronine 5’-deiodination in rat cerebral cortex. Proc. Natl Acad. Sci. USA 79, 5080–5084 (1982)CrossRefPubMedPubMedCentral
41.
A.C. Bianco et al. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endo. Rev. 23, 38–89 (2002)CrossRef
42.
M.J. Berry, L. Banu, P.R. Larsen, Type I iodothyronine deiodinase is a selenocysteine-containing enzyme. Nature 349, 438–440 (1991)CrossRefPubMed
43.
J.C. Davey et al. Cloning of a cDNA for the type II iodothyronine deiodinase. J. Biol. Chem. 270, 26786–26789 (1995)CrossRefPubMed
44.
W. Croteau et al. Cloning of the mammalian type II iodothyronine deiodinase: a selenoprotein differentially expressed and regulated in the human brain and other tissues. J. Clin. Invest. 98, 405–417 (1996)CrossRefPubMedPubMedCentral
45.
M.J. Schneider et al. Targeted disruption of the type 2 selenodeiodinase gene (Dio2) results in a phenotype of pituitary resistance to T4. Mol. Endocrinol. 15, 2137–2148 (2001)CrossRefPubMed
46.
M.J. Schneider et al. Targeted disruption of the type1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 147, 580–589 (2006)CrossRefPubMed
47.
48.
F.R. Crantz, J.E. Silva, P.R. Larsen, An analysis of the sources and quantity of 3,5,3’-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology 110, 367–375 (1982)CrossRefPubMed
49.
K. Sorimachi, J. Robbins, Metabolism of thyroid hormones by cultured monkey hepatocarcinoma cells. Nonphenolic ring dieodination and sulfation. J. Biol. Chem. 252, 4458–4463 (1977)PubMed
50.
51.
S.A. Huang et al. Type 3 iodothyronine deiodinase is highly expressed in the human uteroplacental unit and in fetal epithelium. J. Clin. Endo. Metab. 88, 1384–1388 (2003)CrossRef
52.
L. Ng et al. A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme, in cochlear development and auditory function. Endocrinology 150, 1952–1960 (2009)CrossRefPubMed
53.
D.L. St. Germain et al. A thyroid hormone regulated gene in Xenopus laevis encodes a type III iodothyronine 5-deiodinase. Proc. Natl Acad. Sci. USA 91, 7767–7771 (1994).CrossRef
54.
W. Croteau et al. Cloning and expression of a cDNA for a mammalian type III iodothyronine deiodinase. J. Biol. Chem. 270, 16569–16575 (1995)CrossRefPubMed
55.
A. Hernandez et al. Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis. Endocrinology 148, 5680–5687 (2007)CrossRefPubMed
Metadata
Title
The isolation of thyroxine (T4), the discovery of 3,5,3’-triiodothyronine (T3), and the identification of the deiodinases that generate T3 from T4: An historical review
Authors
John C. Morris
Valerie Anne Galton
Publication date
01-10-2019
Publisher
Springer US
Published in
Endocrine / Issue 1/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-01990-1

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