Background: Maintenance of adequate iodide supply to the developing fetus is dependent not only on maternal dietary iodine intake but also on placental iodide transport. The objective of this study was to examine the effects of different pregnancy-associated hormones on the uptake of radioiodide by the placenta and to determine if iodide transporter expression is affected by hormone incubation. Methods: Primary cultures of placental trophoblast cells were established from placentas obtained at term from pre-labor caesarean sections. They were pre-incubated with 17β-estradiol, prolactin, oxytocin, human chorionic gonadotropin (hCG) and progesterone either singly or in combination over 12 h with 125I uptake being measured after 6 h. RNA was isolated from placental trophoblasts and real-time RT-PCR performed using sodium iodide symporter (NIS) and pendrin (PDS) probes. Results: Significant dose response increments in 125I uptake by trophoblast cells (p < 0.01) were observed following incubation with hCG (60% increase), oxytocin (45% increase) and prolactin (32% increase). Although progesterone (50-200 ng/ml) and 17β-estradiol (1,000-15,000 pg/ml) alone produced no significant differences in uptake, they facilitated increased uptake when combined with prolactin or oxytocin, with a combination of all four hormones producing the greatest increase (82%). Increased 125I uptake was accompanied by corresponding increments in NIS mRNA (ratio 1.52) compared to untreated control cells. No significantly increased expression levels of PDS were observed. Conclusions: Pregnancy-associated hormones, particularly oxytocin and hCG, have a role in promoting placental iodide uptake which may protect the fetus against iodine deficiency.

Keywords:
Placenta, Pregnancy, Iodide uptake, Iodide transporters
1.
Glinoer D: The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-433.
2.
Delange F: Iodine deficiency as a cause of brain damage. Postgrad Med J 2001;77:217-220.
3.
Delange F: Screening for congenital hypothyroidism used as an indicator of the degree of iodine deficiency and of its control. Thyroid 1998;8:1185-1192.
4.
Bidart JM, Lacroix L, Evain-Brion D, Caillou B, Lazar V, Frydman R, Bellet D, Filetti S, Schlumberger M: Expression of Na+/I- symporter and Pendred syndrome genes in trophoblast cells. J Clin Endocrinol Metab 2000;85:4367-4372.
5.
Mitchell AM, Manley SW, Morris JC, et al: Sodium iodide symporter (NIS) gene expression in human placenta. Placenta 2001;22:256-258.
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: The sodium-iodide symporter expression in placental tissue at different gestational age: an immunohistochemical study. Clin Endocrinol (Oxf) 2006;65:544-548.
7.
Degrelle SA, Guibourdenche J, Galland F, Bidart JM, Fournier T, Evain-Brion D: Iodide transporters expression in early human invasive trophoblast. Placenta 2013;34:29-34.
8.
Manley SW, Li H, Mortimer RH: The BeWo choriocarcinoma cell line as a model of iodide transport by placenta. Placenta 2005;26:380-386.
9.
Li H, Patel J, Mortimer RH, Richard K: Ontogenic changes in human placental sodium iodide symporter expression. Placenta 2012;33:946-948.
10.
Eskandari S, Loo DD, Dai G, Levy O, Wright EM, Carrasco N: Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. J Biol Chem 1997;272:27230-27238.
11.
Spitzweg C, Joba W, Morris JC, Heufelder AE: Regulation of sodium iodide symporter gene expression in FRTL-5 rat thyroid cells. Thyroid 1999;9:821-830.
12.
Yoshida A, Sasaki N, Mori A, Taniguchi S, Mitani Y, Ueta Y, Hattori K, Sato R, Hisatome I, Mori T, Shigemasa C, Kosugi S: Different electrophysiological character of I-, ClO4-, and SCN- in the transport by Na+/I- symporter. Biochem Biophys Res Commun 1997;231:731-734.
13.
Chan S, Kachilele S, Hobbs E, Bulmer JN, Boelaert K, McCabe CJ, Driver PM, Bradwell AR, Kester M, Visser TJ, Franklyn JA, Kilby MD: Placental iodothyronine deiodinase expression in normal and growth-restricted human pregnancies. J Clin Endocrinol Metab 2003;88:4488-4495.
14.
Schröder-van der Elst JP, van der Heide D, Kastelijn J, Rousset B, Obregón MJ: The expression of the sodium/iodide symporter is up-regulated in the thyroid of fetuses of iodine-deficient rats. Endocrinology 2001;142:3736-3741.
15.
Burns R, O'Herlihy C, Smyth PPA: The placenta: a significant iodine storage organ. Thyroid 2001;5:541-546.
16.
Arturi F, Lacroix L, Presta I, Scarpelli D, Caillou B, Schlumberger M, Russo D, Bidart JM, Filetti S: Regulation by human chorionic gonadotropin of sodium/iodide symporter gene expression in the JAr human choriocarcinoma cell line. Endocrinology 2002;143:2216-2220.
17.
Li H, Richard K, McKinnon B, Mortimer RH: Effect of iodide on hCG, sodium-iodide symporter expression and iodide uptake in BeWo choriocarcinoma cells. J Clin Endocrinol Metab 2007;92:4046-4051.
18.
Cho JY, Léveillé R, Kao R, Rousset B, Parlow AF, Burak WE Jr, Mazzaferri EL, Jhiang SM: Hormonal regulation of radioiodide uptake activity and Na+/I- symporter expression in mammary glands. J Clin Endocrinol Metab 2000;85:2936-2943.
19.
Arturi F, Ferretti E, Presta I, Mattei T, Scipioni A, Scarpelli D, Bruno R, Lacroix L, Tosi E, Gulino A, Russo D, Filetti S: Regulation of iodide uptake and sodium/iodide symporter expression in the mcf-7 human breast cancer cell line. J Clin Endocrinol Metab 2005;90:2321-2326.
20.
Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, Deng HF, Amenta PS, Fineberg S, Pestell RG, Carrasco N: The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 2000;6:871-878.
21.
Smyth PP, Smith DF, Sheehan S, Higgins M, Burns R, O'Herlihy C: Short-term changes in maternal and neonatal urinary iodine excretion. Thyroid 2007;17:219-222.
22.
Petroff MG, Phillips TA, Ka H, Pace JL, Hunt JS: Isolation and culture of term human trophoblast cells. Methods Mol Med 2006;121:203-217.
23.
Ajjan RA, Watson PF, Findlay C, Metcalfe RA, Crisp M, Ludgate M, Weetman AP: The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity. J Endocrinol 1998;158:351-358.
24.
De Groot LJ, Jameson JL (eds): Endocrinology, ed 4. Philadelphia, PA, WB Saunders, 2001.
25.
Braunstein GD, Grodin JM, Vaitukaitis J, Ross GT: Secretory rates of human chorionic gonadotropin by normal trophoblast. Am J Obstet Gynecol 1973;115:447-450.
26.
Kumaresan P, Anandarangam PB, Dianzon W, Vasicka A: Plasma oxytocin levels during human pregnancy and labor as determined by radioimmunoassay. Am J Obstet Gynecol 1974;119:215-223.
27.
Tulchinsky D, Hobel CJ, Yeager E, Marshall JR: Plasma estradiol, estriol, and progesterone in human pregnancy. II. Clinical applications in Rh-isoimmunization disease. Am J Obstet Gynecol 1972;113:766-770.
28.
Tyson JE, Hwang P, Guyda H, Friesen HG: Studies of prolactin secretion in human pregnancy. Am J Obstet Gynecol 1972;113:14-20.
29.
Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, Jhiang SM: Cloning of the human sodium iodide symporter. Biochem Biophys Res Commun 1996;226:339-345.
30.
Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED: Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997;17:411-422.
31.
Terzidou V, Sooranna SR, Kim LU, Thornton S, Bennett PR, Johnson MR: Mechanical stretch up-regulates the human oxytocin receptor in primary human uterine labor. J Clin Endocrinol Metab 2005;90:237-246.
32.
Rossmanith WG, Wolfahrt S, Ecker A, Eberhardt E: The demonstration of progesterone, but not of estrogen, receptors in the developing human placenta. Horm Metab Res 1997;29:604-610.
33.
Shanker YG, Rao AJ: Progesterone receptor expression in the human placenta. Mol Hum Reprod 1999;5:481-486.
34.
Chung K, Allen R: The use of serial human chorionic gonadotropin levels to establish a viable or a nonviable pregnancy. Semin Reprod Med 2008;26:383-390.
35.
Kogai T, Taki K, Brent GA: Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer 2006;13:797-826.
36.
Schmutzler C, Köhrle J: Implications of the molecular characterization of the sodium-iodide symporter (NIS). Exp Clin Endocrinol Diabetes 1998;106(suppl 3):S1-S10.
37.
Cheong SJ, Jang D, Jeong HJ, Lim ST, Sohn MH, Katzenellenbogen JA, Kim DW: Reduction of stimulated sodium iodide symporter expression by estrogen receptor ligands in breast cancer cells. Nucl Med Biol 2011;38:287-294.
38.
Suzuki K, Kimura H, Wu H, Kudo N, Kim WB, Suzuki S, Yoshida A, Caturegli P, Kohn LD: Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells. Biochem Biophys Res Commun 2010;393:286-290.
39.
Leung AM, Pearce EN, Braverman LE: Perchlorate, iodine and the thyroid. Best Pract Res Clin Endocrinol Metab 2010;24:133-141.
40.
Li H, Landers K, Patel J, Richard K, Mortimer RH: Effect of oxygen concentrations on sodium-iodide symporter expression and iodide uptake and hCG expression in human choriocarcinoma BeWo cells. Am J Physiol Endocrinol Metab 2011;300:E1085-E1091.
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2013
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