BACKGROUND: Iodothyronines are charged amino acid derivatives that cannot 
passively cross a phospholipid bilayer. Transport of thyroid hormones across 
plasma membranes is mediated by integral membrane proteins belonging to several 
gene families. These transporters therefore allow or limit access of thyroid 
hormones into brain. Since thyroid hormones are essential for brain development 
and cell differentiation, it is expected that genetic deficiency of such 
transporters would result in neurodevelopmental derangements.
SCOPE OF REVIEW: We introduce concepts of thyroid hormone transport into the 
brain and into brain cells. Important thyroid hormone transmembrane transporters 
are presented along with their expression patterns in different brain cell 
types. A focus is placed on monocarboxylate transporter 8 (MCT8) which has been 
identified as an essential thyroid hormone transporter in humans. Mutations in 
MCT8 underlie one of the first described X-linked mental retardation syndromes, 
the Allan-Herndon-Dudley syndrome.
MAJOR CONCLUSIONS: Thyroid hormone transporter molecules are expressed in a 
developmental and cell type-specific pattern. Any thyroid hormone molecule has 
to cross consecutively the luminal and abluminal membranes of the capillary 
endothelium, enter astrocytic foot processes, and leave the astrocyte through 
the plasma membrane to finally cross another plasma membrane on its way towards 
its target nucleus.
GENERAL SIGNIFICANCE: We can expect more transporters being involved in or 
contributing to in neurodevelopmental or neuropsychiatric disease. Due to their 
expression in cellular components regulating the hypothalamus-pituitary-thyroid 
axis, mutations and polymorphisms are expected to impact on negative feedback 
regulation and hormonal setpoints. This article is part of a Special Issue 
entitled Thyroid hormone signalling.