Sodium/iodide symporter (NIS) gene expression is the limiting step for the onset of thyroid function in the human fetus.
BACKGROUND
Terminal differentiation of the human thyroid is characterized by the onset of follicle formation and thyroid hormone synthesis at 11 gestational weeks (GW).


OBJECTIVE
This study aimed to investigate the ontogeny of thyroglobulin (Tg), thyroid peroxidase (TPO), sodium/iodide symporter (NIS), pendrin (PDS), dual oxidase 2 (DUOX2), thyroid-stimulating hormone receptor (TSHR), and thyroid transcription factor 1 (TITF1), forkhead box E1 (FOXE1), and paired box gene 8 (PAX8) in the developing human thyroid.


METHODS
Thyroid tissues from human embryos and fetuses (7-33 GW; n = 45) were analyzed by quantitative PCR to monitor mRNA expression for each gene and by immunohistochemistry to determine the cellular distribution of TITF1, TSHR, Tg, TPO, NIS, and the onset of T4 production. A broken line regression model was fitted for each gene to compare the loglinear increase in expression before and after the onset of T4 synthesis.


RESULTS
TITF1, FOXE1, PAX8, TSHR, and DUOX2 were stably expressed from 7 to 33 GW. Tg, TPO, and PDS expression was detectable as early as 7 GW and was correlated with gestational age (all, P < 0.01), and the slope of the regression line was significantly different before and after the onset of T4 synthesis at 11 GW (all, P < 0.01). NIS expression appeared last and showed the highest fit by the broken line regression model of all genes (correlation age P < 0.0001, broken line regression P < 0.0001). Immunohistochemical studies detected TITF1, TSHR, and Tg in unpolarized thyrocytes before follicle formation. T(4) and NIS labeling were only found in developing follicles from 11 GW on.


CONCLUSIONS
These results imply a key role of NIS for the onset of human thyroid function.
Szinnai
Gabor
G
Faculty of Medicine René Descartes, Paris V, Site Necker, Institut National de la Santé et de la Recherche Médicale Equipe Mixte 0363, Pediatric Endocrine Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France.
Lacroix
Ludovic
L
Carré
Aurore
A
Guimiot
Fabien
F
Talbot
Monique
M
Martinovic
Jelena
J
Delezoide
Anne-Lise
AL
Vekemans
Michel
M
Michiels
Stefan
S
Caillou
Bernard
B
Schlumberger
Martin
M
Bidart
Jean-Michel
JM
Polak
Michel
M
D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000032:analysis / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011989:Receptors, Thyrotropin / Q000032:analysis; D027981:Symporters / Q000032:analysis / Q000235:genetics*; D013954:Thyroglobulin / Q000032:analysis / Q000235:genetics; D013961:Thyroid Gland / Q000196:embryology*; D000099209:Sodium-Iodide Symporters
D007453:Iodide Peroxidase; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D027981:Symporters; D013954:Thyroglobulin; D000099209:Sodium-Iodide Symporters