Physiology · Reproductive Physiology

The LH surge that triggers ovulation occurs approximately 24-36 hours before follicular rupture. This midcycle LH surge is paradoxically triggered by estrogen through positive feedback, opposite to the usual negative feedback. This switch from negative to positive feedback requires:

  • A A threshold estrogen level (>200 pg/mL) sustained for at least 36-48 hours, which causes upregulation of GnRH receptors on gonadotrophs and priming of the pituitary to respond with a massive LH surge
  • B A progesterone surge from the dominant follicle that overrides estrogen-mediated negative feedback
  • C A rise in inhibin B that suppresses FSH while allowing LH to rise
  • D Withdrawal of dopaminergic inhibition from GnRH neurons at midcycle specifically triggered by estrogen
Correct answer: A. A threshold estrogen level (>200 pg/mL) sustained for at least 36-48 hours, which causes upregulation of GnRH receptors on gonadotrophs and priming of the pituitary to respond with a massive LH surge

Explanation

The switch from estrogen negative feedback (during follicular phase at low estrogen levels) to positive feedback (midcycle LH surge) requires a specific estradiol concentration threshold (typically >200 pg/mL, in some studies >150 pg/mL for 36-50 hours). Sustained high estradiol upregulates GnRH receptor expression on pituitary gonadotrophs, increases their sensitivity and secretory capacity, and possibly augments GnRH pulse amplitude from kisspeptin-stimulated neurons. The result is a massive (~10-fold) LH surge far exceeding the FSH surge, triggering follicular rupture. Small amounts of progesterone from the mature follicle before ovulation do amplify the LH surge (positive feedback by progesterone at the pituitary level), but the primary mechanism is the high estradiol threshold-duration requirement.

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

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