It was a widely held belief that sex steroids, namely testosterone and 17β-estradiol (E2) of gonadal origin, control synaptic plasticity in the hippocampus. A new paradigm emerged when it was shown that these sex steroids are synthesized in the hippocampus. The inhibition of sex steroids in the hippocampus impairs synaptic plasticity sex-dependently in this region of the brain. In gonadectomized animals and in hippocampal cultures, inhibition of estradiol synthesis in female animals and in cultures from female animals, and inhibition of dihydrotestosterone synthesis in male animals and in cultures of male animals, cause synapse loss and impair LTP in the hippocampus, but not vice versa. Since the hippocampal cultures originated from perinatal animals, and due to the similarity of in vivo and in vitro findings, it appears that hippocampal neurons are differentiated in a sex-specific manner during the perinatal period when sexual imprinting takes place.
