Skip to main content
SpringerLink
Log in

Na+/I− Symporter and Type 3 Iodothyronine Deiodinase Gene Expression in Amniotic Membrane and Placenta and Its Relationship to Maternal Thyroid Hormones

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Placental type 3 iodothyronine deiodinase (D3) potentially protects the fetus from the elevated maternal thyroid hormones. Na+/I− symporter (NIS) is a plasma membrane glycoprotein, which mediates active iodide uptake. Our objectives were to establish the distribution of NIS and D3 gene expressions in the placenta and the amniotic membrane and to investigate the relationship between placental D3 and NIS gene expressions and maternal iodine, selenium, and thyroid hormone status. Thyroid hormones, urinary iodine concentration (UIC), and selenium levels were measured in 49 healthy term pregnant women. NIS and D3 gene expressions were studied with the total mRNA RT-PCR method in tissues from maternal placenta (n = 49), fetal placenta (n = 9), and amniotic membrane (n = 9). NIS and D3 gene expressions were shown in the fetal and maternal sides of the placenta and amniotic membrane. Mean blood selenium level was 66 ± 26.5 μg/l, and median UIC was 143 μg/l. We could not demonstrate any statistically significant relationship of spot UIC and blood selenium with NIS and D3 expression (p > 0.05). Positive correlations were found between NIS and thyroxine-binding globulin (TBG) (r = 0.3, p = 0.042) and between D3 and preoperative glucose levels (r = 0.4, p = 0.006). D3 and NIS genes are expressed in term placenta and amniotic membrane; thus, in addition to placenta, amniotic membrane contributes to regulation of maternofetal iodine and thyroid hormone transmission. Further studies are needed to clarify the relationship between maternal glucose levels and placental D3 expression and between TBG and placental NIS expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. St Germain DL, Galton VA, Hernandez A (2009) Minireview: Defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology 150:1097–1107

    Article  PubMed  CAS  Google Scholar 

  2. Li H, Richard K, McKinnon B, Mortimer RH (2007) Effect of iodide on human choriogonadotropin, sodium-iodide symporter expression, and iodide uptake in BeWo choriocarcinoma cells. J Clin Endocrinol Metab 92:4046–4051

    Article  PubMed  CAS  Google Scholar 

  3. Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, Deng HF, Amenta PS, Fineberg S, Pestell RG, Carrasco N (2000) The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 6:871–878

    Article  PubMed  CAS  Google Scholar 

  4. Riedel C, Dohan O, De la Vieja A, Ginter CS, Carrasco N (2001) Journey of the iodide transporter NIS: from its molecular identification to its clinical role in cancer. Trends Biochem Sci 26:490–496

    Article  PubMed  CAS  Google Scholar 

  5. Bizhanova A, Kopp P (2009) Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology 150:1084–1090

    Article  PubMed  CAS  Google Scholar 

  6. Di Cosmo C, Fanelli G, Tonacchera M, Ferrarini E, Dimida A, Agretti P, De Marco G, Vitti P, Pinchera A, Bevilacqua G, Naccarato AG, Viacava P (2006) The sodium-iodide symporter expression in placental tissue at different gestational age: an immunohistochemical study. Clin Endocrinol (Oxf) 65:544–548

    Article  Google Scholar 

  7. Bidart JM, Lacroix L, Evain-Brion D, Caillou B, Lazar V, Frydman R, Bellet D, Filetti S, Schlumberger M (2000) Expression of Na+/I− symporter and Pendred syndrome genes in trophoblast cells. J Clin Endocrinol Metab 85:4367–4472

    Article  PubMed  CAS  Google Scholar 

  8. Riedel C, Levy O, Carrasco N (2001) Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin. J Biol Chem 15:21458–21463

    Article  Google Scholar 

  9. Schroder-van der Elst JP, van der Heide D, Kastelijn J, Rousset B, Obregon MJ (2001) The expression of the sodium/iodide symporter is up-regulated in the thyroid of fetuses of iodine-deficient rats. Endocrinology 142:3736–3741

    Article  PubMed  CAS  Google Scholar 

  10. Carvalho DP (2003) Modulation of uterine iodothyronine deiodinases—a critical event for fetal development? Endocrinology 144:4250–4252

    Article  PubMed  CAS  Google Scholar 

  11. Galton VA, Martinez E, Hernandez A, St Germain EA, Bates JM, St Germain DL (1999) Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase. J Clin Invest 103:979–987

    Article  PubMed  CAS  Google Scholar 

  12. Mortimer R, Galligan JP, Cannell GR, Addison RS, Roberts MS (1996) Maternal to fetal thyroxine transmission in the human term placenta is limited by inner ring deiodination. J Clin Endocrinol Metab 81:2247–2249

    Article  PubMed  CAS  Google Scholar 

  13. Huang SA, Dorfman DM, Genest DR, Salvatore D, Larsen PR (2003) Type 3 iodothyronine deiodinase is highly expressed in the human uteroplacental unit and in fetal epithelium. J Clin Endocrinol Metab 88:1384–1388

    Article  PubMed  CAS  Google Scholar 

  14. Wasco EC, Martinez E, Grant KS, St Germain EA, St Germain DL, Galton VA (2003) Determinants of iodothyronine deiodinase activities in rodent uterus. Endocrinology 144:4253–4261

    Article  PubMed  CAS  Google Scholar 

  15. Kester MH, Kuiper GG, Versteeg R, Visser TJ (2006) Regulation of type III iodothyronine deiodinase expression in human cell lines. Endocrinology 147:5845–5854

    Article  PubMed  CAS  Google Scholar 

  16. Bates JM, Spate VL, Morris JS, St Germain DL, Galton VA (2000) Effects of selenium deficiency on tissue selenium content, deiodinase activity, and thyroid hormone economy in the rat during development. Endocrinology 141:2490–2500

    Article  PubMed  CAS  Google Scholar 

  17. Chanoine JP, Alex S, Stone S, Fang SL, Veronikis I, Leonard JL, Braverman LE (1993) Placental 5-deiodinase activity and fetal thyroid hormone economy are unaffected by selenium deficiency in the rat. Pediatr Res 34:288–292

    Article  PubMed  CAS  Google Scholar 

  18. Knudsen N, Bols B, Bülow I, Jørgensen T, Perrild H, Ovesen L, Laurberg P (1999) Validation of ultrasonography of the thyroid gland for epidemiological purposes. Thyroid 9:1069–1074

    Article  PubMed  CAS  Google Scholar 

  19. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W (2011) Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21:1081–1125

    Article  PubMed  Google Scholar 

  20. Rayburn WF, Robinson A, Braverman LE, He XM, Pino S, Gargas ML, Kinzell JH (2008) Iodide concentrations in matched maternal serum, cord serum, and amniotic fluid from preterm and term human pregnancies. Reprod Toxicol 25:129–132

    Article  PubMed  CAS  Google Scholar 

  21. García-Fuentes E, Gallo M, García L, Prieto S, Alcaide-Torres J, Santiago P, Velasco I, Soriguer F (2008) Amniotic fluid iodine concentrations do not vary in pregnant women with varying iodine intake. Br J Nutr 99:1178–1181

    Article  PubMed  Google Scholar 

  22. Roti E, Fang SL, Green K, Braverman LE, Emerson CH (1983) Inner ring deiodination of thyroxine and 3,5,3′-triiodothyronine by human fetal membranes. Am J Obstet Gynecol 147:788–792

    PubMed  CAS  Google Scholar 

  23. Schröder-van der Elst JP, van der Heide D, Morreale de Escobar G, Obregón MJ (1998) Iodothyronine deiodinase activities in fetal rat tissues at several levels of iodine deficiency: a role for the skin in 3,5,3′-triiodothyronine economy? Endocrinology 139:2229–2234

    Article  PubMed  Google Scholar 

  24. Glinoer D (1997) The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 18:404–433

    Article  PubMed  CAS  Google Scholar 

  25. Glinoer D (2007) The importance of iodine nutrition during pregnancy. Public Health Nutr 10:1542–1546

    Article  PubMed  Google Scholar 

  26. Schussler GC (2000) The thyroxine-binding proteins. Thyroid 10:141–149

    Article  PubMed  CAS  Google Scholar 

  27. Ekins RP, Sinha AK, Pickard MR, Evans IM, al Yatama F (1994) Transport of thyroid hormones to target tissues. Acta Med Austriaca 21:26–34

    PubMed  CAS  Google Scholar 

  28. Emerson CH, Bambini G, Alex S, Castro MI, Roti E, Braverman LE (1988) The effect of thyroid dysfunction and fasting on placenta inner ring deiodinase activity in the rat. Endocrinology 122:809–816

    Article  PubMed  CAS  Google Scholar 

  29. Chidakel A, Mentuccia D, Celi FS (2005) Peripheral metabolism of thyroid hormone and glucose homeostasis. Thyroid 15:899–903

    Article  PubMed  CAS  Google Scholar 

  30. Medina MC, Molina J, Gadea Y, Fachado A, Murillo M, Simovic G, Pileggi A, Hernández A, Edlund H, Bianco AC (2011) The thyroid hormone-inactivating type III deiodinase is expressed in mouse and human {beta}-cells and its targeted inactivation impairs insulin secretion. Endocrinology 152:3717–3727

    Article  PubMed  CAS  Google Scholar 

  31. Liberman CS, Pino SC, Fang SL, Braverman LE, Emerson CH (1998) Circulating iodide concentrations during and after pregnancy. J Clin Endocrinol Metab 83:3545–3549

    Article  PubMed  CAS  Google Scholar 

  32. Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, Mandel SJ, Stagnaro-Green A (2007) Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 92:S1–S47

    Article  PubMed  CAS  Google Scholar 

  33. Erdoğan MF, Ağbaht K, Altunsu T, Ozbas S, Yücesan F, Tezel B, Sargın C, Ilbeğ I, Artık N, Köse R, Erdoğan G (2009) Current iodine status in Turkey. J Endocrinol Invest 32:617–622

    PubMed  Google Scholar 

  34. Ozdemir HS, Karadas F, Pappas AC, Cassey P, Oto G, Tuncer O (2008) The selenium levels of mothers and their neonates using hair, breast milk, meconium, and maternal and umbilical cord blood in Van Basin. Biol Trace Elem Res 122:206–215

    Article  PubMed  CAS  Google Scholar 

  35. Kilinc M, Guven MA, Ezer M, Ertas IE, Coskun A (2008) Evaluation of serum selenium levels in Turkish women with gestational diabetes mellitus, glucose intolerants, and normal controls. Biol Trace Elem Res 123:35–40

    Article  PubMed  CAS  Google Scholar 

  36. Rayman MP (2002) The argument for increasing selenium intake. Proc Nutr Soc 61:203–215

    Article  PubMed  CAS  Google Scholar 

  37. Izquierdo Alvarez S, Castañón SG, Ruata ML, Aragüés EF, Terraz PB, Irazabal YG, González EG, Rodríguez BG (2007) Updating of normal levels of copper, zinc and selenium in serum of pregnant women. J Trace Elem Med Biol 21:49–52

    Article  PubMed  CAS  Google Scholar 

  38. Ramauge M, Pallud S, Esfandiari A, Gavaret J, Lennon A, Pierre M, Courtin F (1996) Evidence that type III iodothyronine deiodinase in rat astrocyte is a selenoprotein. Endocrinology 137:3021–3025

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project (106S229/SBAG-3475) was supported by TUBITAK (Scientific and Technical Research Council of Turkey). We gratefully acknowledge Prof. Murat Erdogan for the help in UIC analysis and Elif H. Kamber for the technical assistance of the genetic analysis.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Besevler, 06500, Ankara, Turkey

    Mujde Akturk

  2. Department of Obstetrics, Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey

    Ayla Sargin Oruc & Nuri Danisman

  3. Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey

    Serap Erkek & Uygar Halis Tazebay

  4. Division of Biochemistry, Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey

    Umran Buyukkagnici

  5. Division of Radiology, Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey

    Elmas Unlu

  6. Gebze Institute of Technology, Department of Molecular Biology and Genetics, Gebze, 41400, Kocaeli, Turkey

    Uygar Halis Tazebay

Authors
  1. Mujde Akturk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayla Sargin Oruc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nuri Danisman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Serap Erkek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Umran Buyukkagnici
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elmas Unlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Uygar Halis Tazebay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mujde Akturk.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akturk, M., Oruc, A.S., Danisman, N. et al. Na+/I− Symporter and Type 3 Iodothyronine Deiodinase Gene Expression in Amniotic Membrane and Placenta and Its Relationship to Maternal Thyroid Hormones. Biol Trace Elem Res 154, 338–344 (2013). https://doi.org/10.1007/s12011-013-9748-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-013-9748-y

Keywords

Search

Navigation