Meal-related gastrointestinal signals are paracrinally sensed by vagal afferent neurons (VAN), and the signals are projected secondary neurons located in the hindbrain, NTS and AP. The signals are integrated and conducted to high-order neurons, including PBN or nuclei in the mid-brain region, which regulates feeding behavior. Other than the paracrine pathway, gastrointestinal satiety signals are mediated by hormonal pathway and acting in the central nervous system (CNS). Circulating estradiol that secreted from ovary acting on both VAN and the nuclei located in the CNS modulates the responsiveness to gastrointestinal satiety signals. NTS, nucleus of the solitary tract; AP, area postrema; PBN, parabrachial nuclei.