Kisspeptin (KP) neurons of the hypothalamic arcuate nucleus are critical for the pubertal activation of the GnRH pulse generator. Which statement best describes the neuroendocrine integration involving kisspeptin?

• A Kisspeptin neurons are stimulated by leptin and inhibited by estradiol through classical negative feedback
• B KNDy neurons (kisspeptin/neurokinin B/dynorphin) in the arcuate nucleus generate the GnRH pulse via auto-regulatory oscillations; neurokinin B drives synchronization while dynorphin terminates the pulse ✓
• C Kisspeptin acts directly on pituitary gonadotrophs to stimulate LH release, bypassing GnRH
• D Leptin inhibits kisspeptin neurons, explaining amenorrhea in obesity

Explanation

KNDy neurons co-express kisspeptin, neurokinin B (NKB), and dynorphin in the arcuate nucleus. They form a self-regulating oscillatory network: NKB acts on NKB receptors (NK3R) on adjacent KNDy neurons to synchronize kisspeptin release (pulse initiation), while dynorphin acts on kappa-opioid receptors to terminate the pulse. This generates episodic kisspeptin release driving GnRH pulses. Kisspeptin acts exclusively on GnRH neurons (via Kiss1R), not directly on pituitary. Leptin stimulates (not inhibits) kisspeptin neurons, which is why starvation-related hypoleptinemia reduces GnRH pulsatility. Estradiol inhibits arcuate KNDy neurons (negative feedback) but stimulates anteroventral periventricular (AVPV) kisspeptin neurons (positive feedback for LH surge).

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

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