Androgens and the developing hippocampus

The hippocampus is central to spatial learning and stress responsiveness, both of which differ in form and function in males versus females, yet precisely how the hippocampus contributes to these sex differences is largely unknown. In reproductively mature individuals, sex differences in the steroid hormone milieu undergirds many sex differences in hippocampal-related endpoints. However, there is also evidence for developmental programming of adult hippocampal function, with a central role for androgens as well as their aromatized byproduct, estrogens. These include sex differences in cell genesis, synapse formation, dendritic arborization, and excitatory/inhibitory balance. Enduring effects of steroid hormone modulation occur during two developmental epochs, the first being the classic perinatal critical period of sexual differentiation of the brain and the other being adolescence and the associated hormonal changes of puberty. The cellular mechanisms by which steroid hormones enduringly modify hippocampal form and function are poorly understood, but we here review what is known and highlight where attention should be focused.