Schematic of intracellular mechanisms underlying E₂ effects on sexual and social behavior, energy homeostasis, and many other brain-mediated functions. Most of these functions occur as a result of gene transcription elicited by binding of E₂ to the classic ERα and ERβ. The newly characterized mER (Qiu et al., 2006) that seems to mediate some of the effects of E₂ on energy homeostasis opens new possibilities in the investigation of the role of E₂ in normal physiology.