Thyroid hormone (T₃) acts via nuclear receptors (TRα and TRβ). The unliganded TR-β is bound to a thyroid hormone response element (TRE) in a complex with a corepressor. When T₃ binds, the receptor undergoes conformational change causing:
- A Dissociation of the TR from DNA, allowing RNA polymerase direct promoter access
- B Exchange of corepressor for coactivator complex, promoting histone acetylation and increased gene transcription ✓
- C Translocation of the receptor to the mitochondria to directly stimulate oxidative phosphorylation
- D Activation of adenylyl cyclase through Gs protein coupling
Explanation
Unliganded TRβ bound to TRE recruits co-repressors (N-CoR, SMRT) that attract histone deacetylases (HDACs), keeping chromatin condensed and target genes repressed. T₃ binding causes a conformational change (helix 12 repositioning) in the ligand-binding domain that releases co-repressors and recruits co-activators (SRC-1, CBP/p300) with histone acetyltransferase activity, opening chromatin and increasing transcription of target genes (e.g., Na⁺/K⁺-ATPase, β-MHC, SERCA). This genomic mechanism has a delayed onset (hours) compared to non-genomic T₃ effects on mitochondria.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.