Document Detail

Ontogeny of iodothyronine deiodinases in human liver.
MedLine Citation:
PMID:  9709961     Owner:  NLM     Status:  MEDLINE    
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 microM [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 microM 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 microM; 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.
K Richard; R Hume; E Kaptein; J P Sanders; H van Toor; W W De Herder; J C den Hollander; E P Krenning; T J Visser
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  83     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-09-02     Completed Date:  1998-09-02     Revised Date:  2010-08-25    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2868-74     Citation Subset:  AIM; IM    
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
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MeSH Terms
Blotting, Northern
Chromatography, High Pressure Liquid
Dithiothreitol / metabolism
Gestational Age
Infant, Newborn
Infant, Premature
Iodide Peroxidase / metabolism*
Liver / embryology*,  enzymology*,  growth & development
Microsomes, Liver / enzymology
Middle Aged
Propylthiouracil / pharmacology
Triiodothyronine / metabolism
Triiodothyronine, Reverse / metabolism
Grant Support
//Wellcome Trust
Reg. No./Substance:
3483-12-3/Dithiothreitol; 51-52-5/Propylthiouracil; 5817-39-0/Triiodothyronine, Reverse; 6893-02-3/Triiodothyronine; EC Peroxidase

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