Control of thyroid hormone action in the developing rat brain.

Thyroid hormones play important roles in brain development. The physiologic function of thyroid hormones in the developing brain is to provide a timing signal that leads to the induction of differentiation and maturation programs during precise stages of development. Inappropriate initiation of these timing events leads to asynchrony in developmental processes and a deleterious outcome. The developing brain is protected from premature thyroid hormone signaling through a variety of measures. Firstly, local brain levels of both thyroxine and triiodothyronine are controlled by ontogenically regulated patterns of production and metabolism. Secondly, developmentally regulated expression of nuclear proteins involved with the nuclear TH response apparatus control the temporal response of brain genes to thyroid hormone. Finally, developmental regulation of TH action modulating transcription factor expression also controls TH action in the developing brain. Together these molecular mechanisms cooperatively act to temporally control TH action during brain development. A description of these controlling mechanisms is the subject of this review.