Schematic diagram showing proposed activation of RP3V kisspeptin neurons by E2 from birth. In the initial phase up until the mid-prepubertal period, there is no kisspeptin expression (represented by pink bar at bottom). With increasing exposure to E2, kisspeptin expression begins and facilitates GnRH neuron activation. By puberty onset, the kisspeptin expression is fully developed and functioning to amplify GnRH neuron activity. After puberty, kisspeptin expression in the RP3V fluctuates with cyclical E2 levels where it facilitates the generation of the preovulatory GnRH/LH surge in each cycle. GABA, γ-Aminobutyric acid; glu, glutamate.