The actions of thyroid hormone signaling in the nucleus

Thyroid hormones are a critical regulator of mammalian physiology. Much of their action is due to effects in the nucleus where T3 engages thyroid hormone receptor isoforms to mediate its effects. In order to function properly the TR isoforms must be recruited to regulatory sequences within genes that they up-regulate. On these positive regulated target genes the TR can activate or repress depending upon whether the receptor is bound to T3 or not and the type of co-regulatory proteins present in that cell type. In contrast to T3 mediated activation, the mechanism by which the TR represses transcription in the presence of T3 remains unclear. Herein we will review the components of the transcriptional response to T3 within the nucleus and attempt to highlight the outstanding questions in the field.