Endocrine Abstracts (2004) 7 OC9

The expression of monocarboxylate transporter 8, as a specific thyroid hormone transporter in human fetal brain and placenta: the effects of intrauterine growth restriction (IUGR)

SY Chan1, CJ McCabe2, K Boelaert2, TJ Visser3, EC Friesema3, JA Franklyn2 & MD Kilby1

1Division of Reproductive and Child Health, University of Birmingham, UK; 2Division of Medical Sciences, University of Birmingham, Birmingham, UK; 3Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.

Intrauterine growth restriction (IUGR) is a significant cause of perinatal morbidity, in particular neurodevelopmental delay, and is associated with fetal hypothyroxinemia. Thyroid hormone is essential for the optimal development of the central nervous system (CNS) in the fetus. Transport of the active ligand triiodothyronine (T3) across the cell membrane is required for its biological effects, initiated by binding of T3 to nuclear thyroid receptors (TR). Recently, the membrane protein monocarboxylate transporter 8 (MCT8) has been identified as a specific thyroid hormone transporter. Furthermore, mutations in the MCT8 gene have been associated with cases of severe neurodevelopmental delay in childhood. We compared mRNA expression of MCT8 in human fetal cerebral cortex (n=70; obtained by surgical termination of pregnancy between 7 - 20 weeks) with adult cortex (n=11) through TaqMan RT-PCR. Further, we compared MCT8 mRNA expression in villous placenta (n=83) with a cohort of pregnancies with early-onset (25-34 wks; n=9) and late-onset (37-40 wks; n=4) IUGR. In human fetal cortex, there was abundant expression of MCT8 mRNA, which was present from 7 weeks of gestation. Expression did not alter significantly with gestation, and was similar to that of adult cortex. In villous placenta, MCT8 mRNA was present from 6 weeks. Expression was relatively low in the first trimester but significantly increased by 37-40 weeks (P<0.05). In placentae of IUGR pregnancies, MCT mRNA was significantly increased (P<0.05) compared to placentae of appropriately grown fetuses. Conclusion: mRNA encoding MCT8 is expressed in human fetal brain and placenta from the first trimester. The increased expression of MCT8 in placentae of pregnancies complicated by IUGR may represent a homeostatic response to fetal hypothyroxinemia in these pregnancies, by promoting enhanced transplacental passage of T3.

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