Figure 7.

Schematic illustration of E2-ERβ signaling in GnRH neurons at proestrus afternoon and its proposed action on presynaptic GABA and glutamate release. E2 activates the phosphorylation of neuronal NO synthase (nNOS) via ERβ and the Src/PI3K/Akt signal transduction pathway resulting in increased NO production. NO then binds to its receptor, sGC, which is present in both GABAergic and glutamatergic afferent boutons of GnRH neurons. The process increases the release of GABA and glutamate that facilitates the activity of GnRH neurons via GABA_A-R and AMPA/kainate-R.