A patient with Cushing's disease undergoes curative transsphenoidal adenomectomy. Postoperatively, the patient requires glucocorticoid replacement for 12 months before the HPA axis recovers. Which statement best distinguishes the mechanism of cortisol feedback at the pituitary corticotroph from that at the hypothalamic paraventricular nucleus?
- A Pituitary feedback inhibits ACTH secretion within minutes via non-genomic mechanisms; hypothalamic feedback reduces CRH synthesis over hours to days via genomic mechanisms ✓
- B Pituitary feedback suppresses POMC gene transcription only; hypothalamic feedback suppresses CRH release only
- C Pituitary feedback operates via short-loop ACTH inhibition; hypothalamic feedback operates via long-loop cortisol inhibition
- D Pituitary feedback is mediated by membrane glucocorticoid receptors and is rapid; hypothalamic feedback is mediated by nuclear receptors and is slow
Correct answer: A. Pituitary feedback inhibits ACTH secretion within minutes via non-genomic mechanisms; hypothalamic feedback reduces CRH synthesis over hours to days via genomic mechanisms
Explanation
Cortisol feedback on the pituitary occurs rapidly (minutes) through non-genomic membrane effects that reduce ACTH secretion, while hypothalamic CRH suppression requires hours to days via glucocorticoid receptor-mediated genomic inhibition of CRH gene transcription. This distinction explains why the pituitary corticotroph recovers CRH responsiveness faster than CRH neurons resume normal firing after chronic hypercortisolism resolves. Short-loop feedback refers to ACTH inhibiting the hypothalamus, not the pituitary itself.
Reference: Ganong's Review of Medical Physiology, 26th ed.
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Written and medically reviewed by the StethoPrep medical team.