The LH surge at midcycle triggers ovulation. The positive feedback loop of estradiol leading to the LH surge is mediated through which hypothalamic neuronal population?

• A Arcuate nucleus KNDy neurons expressing ER-alpha; rising estradiol directly stimulates arcuate kisspeptin release
• B Anteroventral periventricular (AVPV) kisspeptin neurons expressing ER-alpha; rising late follicular estradiol stimulates AVPV kisspeptin surge, which drives GnRH pulse amplitude increase, causing the LH surge ✓
• C GnRH neurons directly expressing ER-alpha; estradiol directly stimulates GnRH neurons to pulse rapidly
• D Paraventricular nucleus CRH neurons expressing ER-beta; estradiol stimulates CRH which cross-reacts with CRH-R on gonadotrophs

Explanation

The preovulatory LH surge is triggered by positive feedback of high sustained estradiol (from the dominant Graafian follicle) on the hypothalamus. The key site of this positive feedback is the anteroventral periventricular (AVPV) nucleus kisspeptin neurons, which express ER-alpha and are stimulated by estradiol. This is opposite to arcuate KNDy neurons, which are inhibited by estradiol (negative feedback regulating pulse frequency). When sustained late follicular estradiol reaches a threshold, AVPV kisspeptin neurons dramatically increase kisspeptin output → large GnRH pulse → massive LH surge. GnRH neurons themselves lack ER-alpha and cannot respond directly to estradiol; they require kisspeptin intermediaries. This dichotomous kisspeptin system (arcuate negative feedback + AVPV positive feedback) explains cycle control.

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

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