Estrogen acting on mER conducts the leptin-independent JAK/STAT signaling, suggesting that the estrogen and leptin signaling are parallel in mediation of anorexigenic action. In contrast, estrogens synergizes leptin signaling, including JAK/STAT and MAPK, through increases expression of leptin receptor ① and conjugation between mER and tyrosine phosphatase Shp2 ②. LepR, leptin receptor; mER, membrane-associated estrogen receptor.