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.