This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, S. Articles by Kilby, M. D. Search for Related Content PubMed PubMed Citation Articles by Chan, S. Articles by Kilby, M. D.

Placental Iodothyronine Deiodinase Expression in Normal and Growth-Restricted Human Pregnancies

Department of Fetal Medicine, Division of Reproductive and Child Health (S.C., S.K., E.H., M.D.K.), Department of Medical Sciences (K.B., C.J.M., P.M.D., A.R.B., J.A.F.), University of Birmingham, Birmingham, United Kingdom B15 2TG; Department of Pathology, University of Newcastle-upon-Tyne (J.N.B.), Newcastle-upon-Tyne, NE1 4LP United Kingdom; and Department of Internal Medicine III, Erasmus University Medical School (M.K., T.J.V.), 3015 GE Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Prof. Mark Kilby, Department of Fetal Medicine, Division of Reproductive and Child Health, Floor 3, Birmingham Women’s Hospital, University of Birmingham, Edgbaston, Birmingham, United Kingdom B15 2TG. E-mail: m.d.kilby{at}bham.ac.uk.

We have described the expression of specific iodothyronine deiodinase mRNAs (using quantitative RT-PCR) and activities in normal human placentas throughout gestation and compared our findings to those in placentas from pregnancies affected by intrauterine growth restriction (IUGR). The predominant deiodinase expressed in placenta was type III (D3); type II (D2) was also present. In general terms, the activities of the enzymes D2 and D3 (and mRNAs encoding these enzymes) were higher earlier in gestation (<28 wk) than at term and displayed an inverse relationship with the duration of gestation (P < 0.05). Comparison of the relative expressions of mRNAs encoding D2 and D3 as well as their activities in placentas associated with IUGR (early and late gestational groups) with findings from normal placentas of similar gestational ages revealed no significant differences. Immunolocalization of D2 and D3 in syncytiotrophoblast (including syncytial sprouts) and cytotrophoblast of human placentas was demonstrated at both early and late gestation. Treatment of primary cultures of term cytotrophoblast cells in vitro with increasing doses of T₃ (1, 10, and 100 nM) resulted in increased expression of mRNAs encoding both D2 and D3 at 100-nM concentrations (P < 0.01) compared with control. Experiments with JEG-3 choriocarcinoma cells demonstrated a similar effect on D3 mRNA at 10 and 100 nM T₃ (P < 0.01). The demonstrated changes in iodothyronine deiodinase expression in the placenta across pregnancy are likely to contribute to regulation of the thyroid hormone supply to the developing fetus. The lack of difference in deiodinase expression in normal placentas and those found in IUGR argues against placental deiodinases being responsible for the hypothyroxemia in circulating fetal thyroid hormones observed in this condition.

This work was supported by Medical Research Council, United Kingdom; the Wellcome Trust; and the Endowment Fund of the former United Birmingham Hospitals and the Masons Trust.

Abbreviations: CI, Confidence intervals; CNS, central nervous system; D1, deiodinase type I; D2, deiodinase type II; D3, deiodinase type III; FT₃, free T₃; FT₄, free T₄; IUGR, intrauterine growth restriction; PTU, propylthiouracil; TBS, Tris-buffered saline; TR, thyroid hormone receptor.

This article has been cited by other articles:

				S. R. James, J. A. Franklyn, B. J. Reaves, V. E. Smith, S. Y. Chan, T. G. Barrett, M. D. Kilby, and C. J. McCabe Monocarboxylate Transporter 8 in Neuronal Cell Growth Endocrinology, April 1, 2009; 150(4): 1961 - 1969. [Abstract] [Full Text] [PDF]

				G. Canettieri, A. Franchi, M. D. Guardia, I. Morantte, M. G. Santaguida, J. W. Harney, P. R. Larsen, and M. Centanni Activation of Thyroid Hormone Is Transcriptionally Regulated by Epidermal Growth Factor in Human Placenta-Derived JEG3 Cells Endocrinology, February 1, 2008; 149(2): 695 - 702. [Abstract] [Full Text] [PDF]

				S-Y Chan, J A Franklyn, H N Pemberton, J N Bulmer, T J Visser, C J McCabe, and M D Kilby Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction. J. Endocrinol., June 1, 2006; 189(3): 465 - 471. [Abstract] [Full Text] [PDF]

				E. Ferretti, F. Arturi, T. Mattei, A. Scipioni, G. Tell, E. Tosi, I. Presta, R. Morisi, L. Lacroix, A. Gulino, et al. Expression, Regulation, and Function of Paired-Box Gene 8 in the Human Placenta and Placental Cancer Cell Lines Endocrinology, September 1, 2005; 146(9): 4009 - 4015. [Abstract] [Full Text] [PDF]

				S. Y Chan, M. H Andrews, R. Lingas, C. J McCabe, J. A Franklyn, M. D Kilby, and S. G Matthews Maternal nutrient deprivation induces sex-specific changes in thyroid hormone receptor and deiodinase expression in the fetal guinea pig brain J. Physiol., July 15, 2005; 566(2): 467 - 480. [Abstract] [Full Text] [PDF]

				K. J. Barber, J. A. Franklyn, C. J. McCabe, F. L. Khanim, J. N. Bulmer, G. S. J. Whitley, and M. D. Kilby The in Vitro Effects of Triiodothyronine on Epidermal Growth Factor-Induced Trophoblast Function J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1655 - 1661. [Abstract] [Full Text] [PDF]

				J. B. Laoag-Fernandez, H. Matsuo, H. Murakoshi, A. L. Hamada, B. K. Tsang, and T. Maruo 3,5,3'-Triiodothyronine Down-Regulates Fas and Fas Ligand Expression and Suppresses Caspase-3 and Poly (Adenosine 5'-Diphosphate-Ribose) Polymerase Cleavage and Apoptosis in Early Placental Extravillous Trophoblasts in Vitro J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4069 - 4077. [Abstract] [Full Text] [PDF]