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Thyroid hormone regulates the expression of some
brain genes only during specific phases of development. Such
genes are initially unresponsive to T3 (Phase I), become
responsive transiently (Phase II), and are subsequently expressed
in a ligand-independent manner (Phase III).
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The presence of thyroid hormone and T3 receptors in
brain is necessary but not sufficient for gene regulation by T3.
Thyroid hormone regulation of the brain genes tested is not in
general dependent on expression of the TRb1 isoform.
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The ability of nucleoproteins to bind to thyroid
response elements suggests that such proteins may block thyroid
hormone action during Phase 1. The orphan receptor COUP appears
to be one of these nucleoproteins.
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