Most of our knowledge on the mechanisms of thyroid hormone (TH) dependent brain development is based on
clinical observations and animal studies of maternal/fetal hypothyroidism. THs play an essential role in brain
development and hormone deficiency during critical phases in fetal life may lead to severe and permanent brain
damage. Maternal hypothyroidism is considered the most common cause of fetal TH deficiency, but the problem
may also arise in the fetus. In the case of congenital hypothyroidism due to defects in fetal thyroid gland
development or hormone synthesis, clinical symptoms at birth are often mild as a result of compensatory maternal
TH supply. TH transporters (THTs) and deiodinases (Ds) are important regulators of intracellular triiodothyronine (T3)
availability and therefore contribute to the control of thyroid receptors (TRs)-dependent CNS development and
early embryonic life. Defects in fetal THTs or Ds may have more impact on fetal brain since they can result in
intracellular T3 deficiency despite sufficient maternal TH supply. One clear example is the recent discovery of
mutations in the TH transporter (monocarboxylate transporter 8; MCT8) that could be linked to a syndrome of
severe and non reversible psychomotor retardation. Even mild and transient changes in maternal TH levels can
directly affect and alter the gene expression profile, and thus disturb fetal brain development. Animal studies are
needed to increase our understanding of the exact role of THTs and Ds in prenatal brain development.
Ahmed R. G. | Ahmed R. G. | 2259