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Mechanism of thyroid hormone action
Clare B Harvey1, Graham R Williams
1Molecular Endocrinology Group, Division of Medicine & MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Hospital, London, United Kingdom.
Summary
Thyroid hormone (triiodothyronine [T3]) regulates gene expression via nuclear receptors (TRs) that bind DNA. This review covers TRs, their DNA binding sites (TREs), and mechanisms of gene regulation, including novel non-genomic actions.
Area of Science:
- Molecular Endocrinology
- Gene Regulation
- Nuclear Receptor Signaling
Background:
- Thyroid hormone (triiodothyronine [T3]) is crucial for regulating gene expression.
- This regulation occurs through high-affinity nuclear receptors known as thyroid hormone receptors (TRs).
- TRs bind to specific DNA sequences called thyroid hormone response elements (TREs) in gene promoters.
Purpose of the Study:
- To review thyroid hormone receptors (TRs) and their binding sites (thyroid hormone response elements [TREs]).
- To elucidate the mechanisms of TR action in both basal and hormone-bound states.
- To explore interacting proteins, cross-talk with other pathways, and potential non-genomic actions of T3.
Main Methods:
- Literature review of existing research on TRs and TREs.
- Analysis of mechanisms of transcriptional regulation by TRs.
- Discussion of protein-protein interactions and signaling pathway cross-talk.
Main Results:
- TRs bind to TREs to modulate transcription of T3-target genes.
- TRs function through distinct conformational changes upon hormone binding.
- Interacting proteins and cross-talk with other signaling pathways influence TR activity.
- Evidence suggests rapid, non-genomic actions of T3 at the cell membrane.
Conclusions:
- Thyroid hormone receptor function is complex, involving DNA binding, protein interactions, and diverse signaling pathways.
- Understanding TRs, TREs, and their associated mechanisms is key to comprehending thyroid hormone action.
- Emerging evidence points to rapid, non-genomic roles for T3, expanding our view of its biological functions.