In the hypothalamic-pituitary-thyroid axis, free T4 exerts negative feedback primarily on which structure, and what is the intracellular mechanism?
- A Hypothalamus; T4 binds TRH receptors on TRH-producing neurons, competitively inhibiting TRH release
- B Pituitary thyrotrophs; T4 is converted to T3 by type 2 deiodinase, and T3 binds nuclear thyroid hormone receptors reducing TSH gene transcription ✓
- C Pituitary thyrotrophs; T4 directly activates cAMP-dependent pathways to suppress TSH exocytosis
- D Anterior pituitary; T4 increases dopamine release, which inhibits TSH secretion
Correct answer: B. Pituitary thyrotrophs; T4 is converted to T3 by type 2 deiodinase, and T3 binds nuclear thyroid hormone receptors reducing TSH gene transcription
Explanation
Pituitary thyrotrophs express type 2 5'-deiodinase, which locally converts circulating T4 to the more potent T3. T3 enters the nucleus and binds thyroid hormone receptors (TRα/TRβ), which then repress transcription of both TSH-α and TSH-β subunit genes. This intrapituitary conversion mechanism means T4 (the dominant circulating hormone) can exert potent feedback without requiring peripheral conversion, making the pituitary a sensitive and rapid sensor of thyroid axis activity.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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