Sex-Dependent Responsiveness of Hippocampal Neurons to Sex Neurosteroids: A Role of Arc/Arg3.1

This study reveals that the immediate early gene Arc/Arg3.1 is upregulated in a sex-dependent manner by sex neurosteroids in hippocampal neurons, with estradiol (E2) increasing its expression in female neurons and dihydrotestosterone (DHT) in male neurons. The upregulation occurs rapidly and is sustained, highlighting the importance of local neurosteroid synthesis for synaptic plasticity and memory formation. Inhibiting E2 synthesis with letrozole abolishes its effect in females, while DHT's effect in males persists even when its synthesis is blocked. These findings underscore the critical role of sex steroids in brain function and suggest sex-specific mechanisms in synaptic plasticity and memory.