Neurons in the female reproductive cycle. The top panel shows a typical cycle of hormone fluctuations with E2 levels peaking as LH surges to then trigger ovulation. Collective work, including specific targeting of AVPVKiss1 neurons, shows that this population is critical for generating an LH surge during high E2 levels for positive feedback (left lower box). Estrogen signaling in ARCKiss1 neurons is important for maximizing the number of continuous estrous cycles: estrus, diestrus, and proestrus. The number of LH pulses or levels of LH are unchanged after deleting ERα in the ARC or ARCKiss1 neurons. Thus, other estrogen-sensitive brain regions, such as the MeA, must contribute to negative feedback when E2 and LH are low (right lower box). Abbreviations: ARC, arcuate nucleus; AVPV, anteroventral periventricular (nucleus); E2, estradiol; ERα, estrogen receptor alpha; FSH, follicle-stimulating hormone; Kiss, kisspeptin; LH, luteinizing hormone; MeA, medial amygdala; MePD, posterodorsal medial amygdala; P, progesterone; VMH, ventromedial hypothalamus.