RT Journal Article
T1 Lack of action of exogenously administered T3 on the fetal rat brain despite expression of the monocarboxylate transporter 8
A1 Grijota Martínez, María Carmen
A1 Díez, Diego
A1 Morreale de Escobar, Gabriella
A1 Bernal, Juan
A1 Morte, Beatriz
AB Mutations of the monocarboxylate transporter 8 gene (MCT8, SLC16A2) cause the Allan-Herndon-Dudley syndrome, an X-linked syndrome of severe intellectual deficit and neurological impairment. Mct8 transports thyroid hormones (T4 and T3), and the Allan-Herndon-Dudley syndrome is likely caused by lack of T3 transport to neurons during critical periods of fetal brain development. To evaluate the role of Mct8 in thyroid hormone action in the fetal brain we administered T4 or T3 to thyroidectomized pregnant dams treated with methyl-mercapto-imidazol to produce maternal and fetal hypothyroidism. Gene expression was then measured in the fetal cerebral cortex. T4 increased Camk4, Sema3c, and Slc7a3 expression, but T3 was without effect. To investigate the cause for the lack of T3 action we analyzed the expression of organic anion transport polypeptide (Oatp14, Slco1c1), a T4 transporter, and Mct8 (Slc16a2), a T4 and T3 transporter, by confocal microscopy. Both proteins were present in the brain capillaries forming the blood-brain barrier and in the epithelial cells of the choroid plexus forming the blood-cerebrospinal fluid barrier. It is concluded that T4 from the maternal compartment influences gene expression in the fetal cerebral cortex, possibly after transport via organic anion transporter polypeptide and/or Mct8, and conversion to T3 in the astrocytes. On the other hand, T3 does not reach the target neurons despite the presence of Mct8. The data indicate that T4, through local deiodination, provides most T3 in the fetal rat brain. The role of Mct8 as a T3 transporter in the fetal rat brain is therefore uncertain.
PB Oxford University Press
SN 0013-7227
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/92381
UL https://hdl.handle.net/20.500.14352/92381
LA eng
NO Grijota-Martínez, Carmen, et al. «Lack of Action of Exogenously Administered T3 on the Fetal Rat Brain Despite Expression of the Monocarboxylate Transporter 8». Endocrinology, vol. 152, n.o 4, abril de 2011, pp. 1713-21.  https://doi.org/10.1210/en.2010-1014.
NO Ministerio de Ciencia e Innovación (España)
NO European Commission
NO Instituto de Salud Carlos III
NO Consejo Superior de Investigaciones Científicas
NO The Japanese Society for the Promotion of Science
DS Docta Complutense
RD 18 abr 2025