help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Richard, K.
Right arrow Articles by Visser, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Richard, K.
Right arrow Articles by Visser, T. J.
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 8 2868-2874
Copyright © 1998 by The Endocrine Society

Original Studies

Ontogeny of Iodothyronine Deiodinases in Human Liver1

Kerry Richard, Robert Hume, Ellen Kaptein, Jo P. Sanders, Hans van Toor, Wouter W. de Herder, Jan C. den Hollander, Eric P. Krenning and Theo J. Visser

Department of Internal Medicine III, Erasmus University Medical School (K.R., E.K., J.P.S., H.v.T., W.W.d.H., E.P.K., T.J.V.), Rotterdam, The Netherlands; Department of Obstetrics and Gynaecology, University of Dundee, Ninewells Hospital and Medical School (K.R., R.H.), Dundee, United Kingdom; Department of Pathology, Erasmus University Medical School (J.C.d.H.), Rotterdam, The Netherlands; and Department of Nuclear Medicine, University Hospital Dijkzigt (E.P.K.), Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Theo J. Visser, Department of Internal Medicine III, Erasmus University Medical School, P.O. Box 1738, Room Bd. 234, 3000 DR Rotterdam, The Netherlands. E-mail: visser{at}inw3.azr.nl

The role of the deiodinases D1, D2, and D3 in the tissue-specific and time-dependent regulation of thyroid hormone bioactivity during fetal development has been investigated in animals but little is known about the ontogeny of these enzymes in humans. We analyzed D1, D2, and D3 activities in liver microsomes from 10 fetuses of 15–20 weeks gestation and from 8 apparently healthy adult tissue transplant donors, and in liver homogenates from 2 fetuses (20 weeks gestation), 5 preterm infants (27–32 weeks gestation), and 13 term infants who survived up to 39 weeks postnatally. D1 activity was determined using 1 µM [3',5'-125I]rT3 as substrate and 10 mM dithiothreitol (DTT) as cofactor, D2 activity using 1 nM [3',5'-125I]T4 and 25 mM DTT in the presence of 1 mM 6-propyl-2-thiouracil (to block D1 activity) and 1 µM T3 (to block D3 activity), and D3 activity using 10 nM [3,5-125I]T3 and 50 mM DTT, by quantitation of the release of 125I-. The assays were validated by high performance liquid chromatography of the products, and kinetic analysis [Michaelis-Menten constant (Km) of rT3 for D1: 0.5 µM; Km of T3 for D3: 2 nM]. In liver homogenates, D1 activity was not correlated with age, whereas D3 activity showed a strong negative correlation with age (r -0.84), with high D3 activities in preterm infants and (except in 1 infant of 35 weeks) absent D3 activity in full-term infants. In microsomes, D1 activities amounted to 4.3–60 pmol/min/mg protein in fetal livers and to 170–313 pmol/min/mg protein in adult livers, whereas microsomal D3 activities were 0.15–1.45 pmol/min/mg protein in fetuses and <0.1 pmol/min/mg protein in all but one adult. In the latter sample, D3 activity amounted to 0.36 pmol/min/mg protein. D2 activity was negligible in both fetal and adult livers. These findings indicate high D1 and D3 activities in fetal human liver, and high D1 and mostly absent D3 activities in adult human liver. Therefore, the low serum T3 levels in the human fetus appear to be caused by high hepatic (and placental) D3 activity rather than caused by low hepatic D1 activity. The occasional expression of D3 in adult human liver is intriguing and deserves further investigation.




This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
K. A. Heemstra, M. R. Soeters, E. Fliers, M. J. Serlie, J. Burggraaf, M. B. van Doorn, A. A. van der Klaauw, J. A. Romijn, J. W. Smit, E. P. Corssmit, et al.
Type 2 Iodothyronine Deiodinase in Skeletal Muscle: Effects of Hypothyroidism and Fasting
J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 2144 - 2150.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. A. Huang
Deiodination and Cellular Proliferation: Parallels between Development, Differentiation, Tumorigenesis, and Now Regeneration
Endocrinology, January 1, 2009; 150(1): 3 - 4.
[Full Text] [PDF]

Home page
 Endocr. Rev.Home page
B. Gereben, A. M. Zavacki, S. Ribich, B. W. Kim, S. A. Huang, W. S. Simonides, A. Zeold, and A. C. Bianco
Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling
Endocr. Rev., December 1, 2008; 29(7): 898 - 938.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. L. Olivares, M. P. Marassi, R. S. Fortunato, A. C. M. da Silva, R. H. Costa-e-Sousa, I. G. Araujo, E. C. Mattos, M. O. Masuda, M. A. Mulcahey, S. A. Huang, et al.
Thyroid Function Disturbance and Type 3 Iodothyronine Deiodinase Induction after Myocardial Infarction in Rats A Time Course Study
Endocrinology, October 1, 2007; 148(10): 4786 - 4792.
[Abstract] [Full Text] [PDF]

Home page
 Annals of Clinical & Laboratory ScienceHome page
A. E. Balazs, I. Athanassaki, S. K. Gunn, N. Tatevian, S. A. Huang, M. W. Haymond, and L. P. Karaviti
Rapid Resolution of Consumptive Hypothyroidism in a Child with Hepatic Hemangioendothelioma Following Liver Transplantation
Ann. Clin. Lab. Sci., January 1, 2007; 37(3): 280 - 284.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. H. A. Kester, G. G. J. M. Kuiper, R. Versteeg, and T. J. Visser
Regulation of Type III Iodothyronine Deiodinase Expression in Human Cell Lines
Endocrinology, December 1, 2006; 147(12): 5845 - 5854.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. Morvan Dubois, A. Sebillot, G. G. J. M. Kuiper, C. H. J. Verhoelst, V. M. Darras, T. J. Visser, and B. A. Demeneix
Deiodinase Activity Is Present in Xenopus laevis during Early Embryogenesis
Endocrinology, October 1, 2006; 147(10): 4941 - 4949.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. J. Visser
The elemental importance of sufficient iodine intake: a trace is not enough.
Endocrinology, May 1, 2006; 147(5): 2095 - 2097.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
M. A. Christoffolete, R. Ribeiro, P. Singru, C. Fekete, W. S. da Silva, D. F. Gordon, S. A. Huang, A. Crescenzi, J. W. Harney, E. C. Ridgway, et al.
Atypical Expression of Type 2 Iodothyronine Deiodinase in Thyrotrophs Explains the Thyroxine-Mediated Pituitary Thyrotropin Feedback Mechanism
Endocrinology, April 1, 2006; 147(4): 1735 - 1743.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Kohrle, F. Jakob, B. Contempre, and J. E. Dumont
Selenium, the Thyroid, and the Endocrine System
Endocr. Rev., December 1, 2005; 26(7): 944 - 984.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. P. Peeters, M. H. A. Kester, P. J. Wouters, E. Kaptein, H. van Toor, T. J. Visser, and G. Van den Berghe
Increased Thyroxine Sulfate Levels in Critically Ill Patients as a Result of a Decreased Hepatic Type I Deiodinase Activity
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6460 - 6465.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. A. Huang, M. A. Mulcahey, A. Crescenzi, M. Chung, B. W. Kim, C. Barnes, W. Kuijt, H. Turano, J. Harney, and P. R. Larsen
Transforming Growth Factor-{beta} Promotes Inactivation of Extracellular Thyroid Hormones via Transcriptional Stimulation of Type 3 Iodothyronine Deiodinase
Mol. Endocrinol., December 1, 2005; 19(12): 3126 - 3136.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Debaveye, B. Ellger, L. Mebis, E. Van Herck, W. Coopmans, V. Darras, and G. Van den Berghe
Tissue Deiodinase Activity during Prolonged Critical Illness: Effects of Exogenous Thyrotropin-Releasing Hormone and Its Combination with Growth Hormone-Releasing Peptide-2
Endocrinology, December 1, 2005; 146(12): 5604 - 5611.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. L. R. Williams, S. A. Ogston, H. van Toor, T. J. Visser, R. Hume, and with collaboration from the Scottish Preterm Thyro
Serum Thyroid Hormones in Preterm Infants: Associations with Postnatal Illnesses and Drug Usage
J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 5954 - 5963.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
P Cettour-Rose, T J Visser, A G Burger, and F Rohner-Jeanrenaud
Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats
Eur. J. Endocrinol., September 1, 2005; 153(3): 429 - 434.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. L. R. Williams, G. J. Mires, C. Barnett, S. A. Ogston, H. van Toor, T. J. Visser, R. Hume, and with collaboration from the Scottish Preterm Thyro
Transient Hypothyroxinemia in Preterm Infants: The Role of Cord Sera Thyroid Hormone Levels Adjusted for Prenatal and Intrapartum Factors
J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4599 - 4606.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Alkemade, E. C. Friesema, U. A. Unmehopa, B. O. Fabriek, G. G. Kuiper, J. L. Leonard, W. M. Wiersinga, D. F. Swaab, T. J. Visser, and E. Fliers
Neuroanatomical Pathways for Thyroid Hormone Feedback in the Human Hypothalamus
J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4322 - 4334.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Morimura, K. Tsunekawa, T. Kasahara, K. Seki, T. Ogiwara, M. Mori, and M. Murakami
Expression of Type 2 Iodothyronine Deiodinase in Human Osteoblast Is Stimulated by Thyrotropin
Endocrinology, April 1, 2005; 146(4): 2077 - 2084.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Kalsbeek, R. M. Buijs, R. van Schaik, E. Kaptein, T. J. Visser, B. Z. Doulabi, and E. Fliers
Daily Variations in Type II Iodothyronine Deiodinase Activity in the Rat Brain as Controlled by the Biological Clock
Endocrinology, March 1, 2005; 146(3): 1418 - 1427.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. L. R. Williams, J. Simpson, C. Delahunty, S. A. Ogston, J. J. Bongers-Schokking, N. Murphy, H. van Toor, S.-Y. Wu, T. J. Visser, R. Hume, et al.
Developmental Trends in Cord and Postpartum Serum Thyroid Hormones in Preterm Infants
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5314 - 5320.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. W. J. S. Wassen, W. Klootwijk, E. Kaptein, D. J. Duncker, T. J. Visser, and G. G. J. M. Kuiper
Characteristics and Thyroid State-Dependent Regulation of Iodothyronine Deiodinases in Pigs
Endocrinology, September 1, 2004; 145(9): 4251 - 4263.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Hume, J. Simpson, C. Delahunty, H. van Toor, S. Y. Wu, F. L. R. Williams, and T. J. Visser
Human Fetal and Cord Serum Thyroid Hormones: Developmental Trends and Interrelationships
J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4097 - 4103.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. H. A. Kester, R. Martinez de Mena, M. Jesus Obregon, D. Marinkovic, A. Howatson, T. J. Visser, R. Hume, and G. Morreale de Escobar
Iodothyronine Levels in the Human Developing Brain: Major Regulatory Roles of Iodothyronine Deiodinases in Different Areas
J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3117 - 3128.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. Murphy, R. Hume, H. van Toor, T. G. Matthews, S. A. Ogston, S.-Y. Wu, T. J. Visser, and F. L. R. Williams
The Hypothalamic-Pituitary-Thyroid Axis in Preterm Infants; Changes in the First 24 Hours of Postnatal Life
J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2824 - 2831.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
D. Konrad, G. Ellis, and K. Perlman
Spontaneous Regression of Severe Acquired Infantile Hypothyroidism Associated With Multiple Liver Hemangiomas
Pediatrics, December 1, 2003; 112(6): 1424 - 1426.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. H. A. Kester, E. Kaptein, T. J. Roest, C. H. van Dijk, D. Tibboel, W. Meinl, H. Glatt, M. W. H. Coughtrie, and T. J. Visser
Characterization of rat iodothyronine sulfotransferases
Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E592 - E598.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. P. Peeters, P. J. Wouters, E. Kaptein, H. van Toor, T. J. Visser, and G. Van den Berghe
Reduced Activation and Increased Inactivation of Thyroid Hormone in Tissues of Critically Ill Patients
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3202 - 3211.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Santini, P. Vitti, L. Chiovato, G. Ceccarini, M. Macchia, L. Montanelli, G. Gatti, V. Rosellini, C. Mammoli, E. Martino, et al.
Role for Inner Ring Deiodination Preventing Transcutaneous Passage of Thyroxine
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2825 - 2830.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. G. J. M. Kuiper, W. Klootwijk, and T. J. Visser
Substitution of Cysteine for Selenocysteine in the Catalytic Center of Type III Iodothyronine Deiodinase Reduces Catalytic Efficiency and Alters Substrate Preference
Endocrinology, June 1, 2003; 144(6): 2505 - 2513.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Friedrichsen, S. Christ, H. Heuer, M. K. H. Schafer, A. Mansouri, K. Bauer, and T. J. Visser
Regulation of Iodothyronine Deiodinases in the Pax8-/- Mouse Model of Congenital Hypothyroidism
Endocrinology, March 1, 2003; 144(3): 777 - 784.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. A. Huang, D. M. Dorfman, D. R. Genest, D. Salvatore, and P. R. Larsen
Type 3 Iodothyronine Deiodinase Is Highly Expressed in the Human Uteroplacental Unit and in Fetal Epithelium
J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1384 - 1388.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. C. van Beeren, W. M. C. Jong, E. Kaptein, T. J. Visser, O. Bakker, and W. M. Wiersinga
Dronerarone Acts as a Selective Inhibitor of 3,5,3'-Triiodothyronine Binding to Thyroid Hormone Receptor-{alpha}1: In Vitro and in Vivo Evidence
Endocrinology, February 1, 2003; 144(2): 552 - 558.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
P. Cettour-Rose, A. G. Burger, C. A. Meier, T. J. Visser, and F. Rohner-Jeanrenaud
Central stimulatory effect of leptin on T3 production is mediated by brown adipose tissue type II deiodinase
Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E980 - E987.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. A. Shepherdley, C. B. Daniels, S. Orgeig, S. J. Richardson, B. K. Evans, and V. M. Darras
Glucocorticoids, thyroid hormones, and iodothyronine deiodinases in embryonic saltwater crocodiles
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2002; 283(5): R1155 - R1163.
[Abstract] [Full Text] [PDF]

Home page
 Arch. Dis. Child. Fetal Neonatal Ed.Home page
A L Ogilvy-Stuart
Neonatal thyroid disorders
Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2002; 87(3): F165 - 171.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. A. Huang, S. A. Fish, D. M. Dorfman, D. Salvatore, H. P. W. Kozakewich, S. J. Mandel, and P. R. Larsen
A 21-Year-Old Woman with Consumptive Hypothyroidism due to a Vascular Tumor Expressing Type 3 Iodothyronine Deiodinase
J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4457 - 4461.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. M. Calvo, E. Jauniaux, B. Gulbis, M. Asuncion, C. Gervy, B. Contempre, and G. Morreale de Escobar
Fetal Tissues Are Exposed to Biologically Relevant Free Thyroxine Concentrations during Early Phases of Development
J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1768 - 1777.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
A. C. Bianco, D. Salvatore, B. Gereben, M. J. Berry, and P. R. Larsen
Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the Iodothyronine Selenodeiodinases
Endocr. Rev., February 1, 2002; 23(1): 38 - 89.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J.-P. Chanoine, J. Nève, S. Wu, J. Vanderpas, and P. Bourdoux
Selenium Decreases Thyroglobulin Concentrations But Does Not Affect the Increased Thyroxine-to-Triiodothyronine Ratio in Children with Congenital Hypothyroidism
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1160 - 1163.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Morreale de Escobar, M. Jesús Obregón, and F. Escobar del Rey
Is Neuropsychological Development Related to Maternal Hypothyroidism or to Maternal Hypothyroxinemia?
J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 3975 - 3987.
[Abstract] [Full Text]

Home page
 NeoReviewsHome page
A. G. van Wassenaer and J. H. Kok
Thyroid Function and Thyroid Hormone Requirements of Very Preterm Infants
NeoReviews, June 1, 2000; 1(6): e116 - 121.
[Full Text]

Home page
 EndocrinologyHome page
J. P. Sanders, S. Van der Geyten, E. Kaptein, V. M. Darras, E. R. Kühn, J. L. Leonard, and T. J. Visser
Cloning and Characterization of Type III Iodothyronine Deiodinase from the Fish Oreochromis niloticus
Endocrinology, August 1, 1999; 140(8): 3666 - 3673.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1998 by The Endocrine Society