Thyroid hormone transporters and deiodinases in the developing human hypothalamus.
OBJECTIVE
Thyroid hormone (TH) signaling in brain cells is dependent on transport of TH across the plasma membrane followed by intracellular deiodination and binding to the nuclear TH receptors. The aim of this study is to investigate the expression of the specific TH transporters monocarboxylate transporter 8 (MCT8 (SLC16A2)), MCT10, organic anion transporting polypeptide 1C1 (OATP1C1 (SLCO1C1)), and the types 2 and 3 deiodinases (D2 and D3) in the developing human hypothalamus.


METHODS
Fifteen postmortem brain samples of fetuses and young children ranging between 17 weeks of gestation and 29 months of postnatal age including one child (28 months) with central congenital hypothyroidism were studied.


METHODS
Sections of the different hypothalami were stained with polyclonal rabbit antisera against MCT8, MCT10, OATP1C1, D2, and D3.


RESULTS
We found MCT8 and D3 but not D2 protein expression to be present in our earliest sample of 17 weeks of gestation, indicating triiodothyronine degradation, but not production at this time of development. At term, expression of TH transporters and D2 decreased and D3 expression increased, suggesting decreased TH signaling just before birth. The child with central congenital hypothyroidism showed higher MCT8 and D2 expression compared with the other children of similar age.


CONCLUSIONS
This study reports the developmental timing of expression of components crucial for central TH signaling in the human hypothalamus. In general, during fetal hypothalamic development, the coordinated expression of D2 and D3 in combination with the different TH transporters suggests that proper TH concentrations are regulated to prevent untimely maturation of brain cells.
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Edith C H
EC
Friesema
Theo J
TJ
Visser
Anke J
AJ
Borgers
Andries
A
Kalsbeek
Dick F
DF
Swaab
Eric
E
Fliers
Anneke
A
Alkemade
D001692:Biological Transport / Q000502:physiology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D000097564:Iodothyronine Deiodinase Type II
D007453:Iodide Peroxidase; D027501:Monocarboxylic Acid Transporters; D027361:Organic Anion Transporters; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II; C117274:iodothyronine deiodinase type III