Mechanism of thyroid hormone action.
Thyroid hormone (triiodothyronine [T3]) regulates gene expression by binding to high-affinity nuclear receptors. Thyroid hormone receptors (TRs) recognize specific response element sequences in the promoters of T3-target genes and activate or repress transcription in response to hormone. In this paper, we review the TR proteins and thyroid hormone response elements (TREs) to which they bind, the mechanisms of action of TRs bound to the TRE in basal and liganded conformations, and the interacting proteins implicated in these complexes. We then briefly consider the cross-talk with other signaling pathways and introduce the idea that T3 may also act rapidly via nongenomic actions located on membranes. We discuss patterns of gene expression and specific actions of the various TR isoforms and consider the novel TR isoform specific ligands.
Harvey
Clare B
CB
Molecular Endocrinology Group, Division of Medicine & MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Hospital, London, United Kingdom.
Williams
Graham R
GR
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020218:Response Elements / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014284:Triiodothyronine / Q000378:metabolism / Q000502:physiology*
D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine