Thyroid hormone (T3) exerts most of its cellular effects through which primary mechanism?
- A T3 enters cells, binds nuclear thyroid hormone receptors (TR alpha and beta) acting as ligand-activated transcription factors that activate or repress thyroid response elements (TREs) in target gene promoters ✓
- B T3 binds cell-surface G-protein coupled receptors, activating adenylyl cyclase to raise cAMP and activate PKA within seconds
- C T3 binds mitochondrial receptors, directly increasing oxidative phosphorylation uncoupling and ATP production
- D T3 acts solely through non-genomic pathways via phosphoinositide-3-kinase (PI3K) activation in the cytoplasm
Explanation
Thyroid hormone (T3, the active form converted from T4 by 5'-deiodinases) exerts most of its effects through nuclear receptors. T3 is lipophilic and enters cells passively (also via specific membrane transporters including MCT8). Inside the nucleus, T3 binds thyroid hormone receptors (TRα and TRβ), which are members of the nuclear receptor superfamily. Unliganded TRs bound to TREs recruit co-repressors; T3 binding causes a conformational change, co-repressors are exchanged for co-activators, and transcription is regulated. Genomic effects include increased synthesis of Na+/K+-ATPase, beta-myosin heavy chain, and uncoupling proteins. Non-genomic effects (option D) exist but are not the primary mechanism. T3 does not use cAMP (option B) as a primary second messenger.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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