During the late follicular phase of the menstrual cycle, rising estrogen levels trigger the LH surge. Which receptor mechanism enables this positive feedback (pro-ovulatory) response of the pituitary to estrogen?

• A High-sustained estrogen (>200 pg/mL for >48 hours) upregulates GnRH receptors on gonadotrophs, amplifying GnRH-stimulated LH secretion
• B Estrogen stimulates kisspeptin (KISS1) neurons in the anteroventral periventricular nucleus (AVPV) to release kisspeptin, which drives the GnRH pulse surge ✓
• C Estrogen directly stimulates LH secretion from anterior pituitary gonadotrophs via a non-GnRH dependent mechanism
• D Estrogen inhibits progesterone receptor expression in gonadotrophs, removing negative feedback

Explanation

The positive feedback of sustained high estrogen works primarily at the hypothalamic level. Estrogen upregulates estrogen receptors on kisspeptin (KISS1) neurons in the anteroventral periventricular nucleus (AVPV) of the hypothalamus — unlike arcuate kisspeptin neurons (which mediate negative feedback). AVPV kisspeptin neurons respond to high estrogen by releasing a surge of kisspeptin → massive pulsatile GnRH release → LH surge → ovulation. Option A contributes at the pituitary level but is secondary. Option C is partially true (estrogen sensitizes gonadotrophs) but is not the primary mechanism. Option D is incorrect.

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

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