Thyroid hormone (T3) exerts its major genomic effects through which mechanism?
- A T3 binds plasma membrane receptor → activates adenylyl cyclase → cAMP-mediated gene transcription
- B T3 binds mitochondrial receptors to directly uncouple oxidative phosphorylation
- C T3 enters the cell, binds nuclear thyroid hormone receptors (TR-α, TR-β), which bind thyroid response elements (TREs) on DNA and regulate gene transcription ✓
- D T3 acts only through non-genomic mechanisms via PI3K pathway; genomic actions require T4 conversion in the nucleus
Correct answer: C. T3 enters the cell, binds nuclear thyroid hormone receptors (TR-α, TR-β), which bind thyroid response elements (TREs) on DNA and regulate gene transcription
Explanation
T3 (the active form) is a lipid-soluble hormone that diffuses into cells and binds to nuclear thyroid hormone receptors (TRα and TRβ — members of the nuclear receptor superfamily). The T3-TR complex binds to thyroid response elements (TREs) on DNA, interacting with coactivators or corepressors to regulate transcription of target genes (e.g., Na+/K+ ATPase, beta-myosin heavy chain, SERCA, LDL receptor, UCP1). T4 is converted to T3 by intracellular deiodinases (mainly D2 in the nucleus). Non-genomic actions also exist but are secondary.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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