During stress, CRH release from the hypothalamic paraventricular nucleus triggers ACTH secretion. Which negative feedback mechanism most rapidly terminates an acute CRH/ACTH surge?

• A Cortisol directly suppresses corticotrophs and PVN CRH neurons via glucocorticoid receptors ✓
• B ACTH itself acts in a short-loop negative feedback on the anterior pituitary
• C Arginine vasopressin, co-secreted with CRH, feeds back to the PVN to reduce further CRH release
• D Somatostatin released from the periventricular nucleus inhibits ACTH secretion directly

Explanation

Cortisol exerts fast, delayed, and slow negative feedback at both the hippocampus/PVN and at anterior pituitary corticotrophs through glucocorticoid receptors (GR). The fast feedback (occurring within minutes) is mediated by non-genomic GR signalling, while delayed and slow feedback involve genomic suppression of CRH and POMC transcription. ACTH short-loop feedback (option B) is a minor modulator. AVP (option C) synergises CRH signalling rather than inhibiting it. Somatostatin (option D) has no direct inhibitory effect on ACTH.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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