Abstract: Hippocampal-derived sex hormones are neuromodulators in the hippocampus. We investigated effects of Estradiol (E2). Adult male hippocampus synthesized 8nM E2. Synaptic estrogen receptors (ERalpha) are in spines of hippocampal neurons. Localization of ERalpha in spines was demonstrated by immunogold electron microscopy. We demonstrated that E2 induced the long-term potentiation (LTP) of the hippocampal neurons by weak theta burst stimulation (sub-threshold stimulation) in hippocampal CA1 pyramidal neurons. E2 rapidly drives PKA, PKC, and MAPK through ERalpha and ERbeta in hippocampal synapses. These kinases may phosphorylate NR2B subunit of NMDA receptor, leading to the increase in calcium influx and CaMKII activation, resulting in induction of LTP. We did not observe participation of mGluR1 in signaling of E2 plus ERalpha. E2 signaling is different between male and female hippocampal neurons.
references :
(1) Ooishi et al., "Estradiol Rapidly Rescues Synaptic Transmission from Corticosterone-induced Suppression via Synaptic/Extranuclear Steroid Receptors in the Hippocampus" Cerebral Cortex (2012)
(2) Kimoto et al., "Semicomprehensive Analysis of the Postnatal Age-Related Changes in the mRNA Expression of Sex Steroidogenic Enzymes and Sex Steroid Receptors in the Male Rat Hippocampus" Endocrinology (2010)
(3) Hojo et al., "Comparison between Hippocampus-Synthesized and Circulation-Derived Sex Steroids in the Hippocampus" Endocrinology (2009)
(4) Hojo et al., "Adult Male Rat Hippocampus Synthesizes Estradiol from Pregnenolone by Cytochromes P45017a and P450 Aromatase Localized in Neurons" Proc. Natl. Acad. Sci. U.S.A. (2004)