Availability and metabolism of thyroid hormones in the developing brain

Thyroid hormones (T3 and T4) are essential for the development and function of the mammalian central nervous system (CNS). For this reason, controlling the availability of thyroid hormones to neural cells is an essential step. This is probably why this is a complex process with several levels of regulation, with the ultimate goal of controlling the appropriate spatial and temporal levels of T3, the nuclear active thyroid hormone, in the CNS. The mechanisms responsible for an appropriate thyroid hormone availability and action during foetal brain development include the expression of thyroid hormone receptors, to which T3 binds to mediate its actions by regulating the expression of T3-target genes; transplacental passage of thyroid hormones to the foetus; expression of transmembrane transporter proteins with the ability to transport thyroid hormones across cell membranes and expression of deiodinase enzymes that can activate (T4 to T3 conversion) or inactivate thyroid hormone action. Lack of thyroid hormone action during brain development can lead to several brain impairments, which functional consequences depend on the timing and the cause for thyroid hormone deficiency.