Category: endocrine_axis
Hypothalamic GnRH neurons fire pulsatile bursts (90-min interpulse interval in adult ♀ follicular phase, faster luteal) under upstream control of kisspeptin/KNDy neurons (arcuate nucleus). GnRH → anterior pituitary gonadotropes → LH + FSH → gonadal sex-steroid synthesis. Pulsatile GnRH stimulates; continuous GnRH desensitizes (paradoxical castration). Therapeutic exploitation: pulsatile GnRH (gonadorelin) for hypothalamic infertility; continuous GnRH agonists (leuprolide, triptorelin, goserelin) → initial flare → desensitization → chemical castration for prostate cancer + central precocious puberty + endometriosis; GnRH antagonists (cetrorelix, ganirelix, degarelix) suppress without flare. Kisspeptin (KISS1 + kisspeptin-10 = KP-10 minimum agonist fragment) directly activates KISS1R on GnRH neurons — research-stage as a GnRH-pulse stimulator.