Fig. 2

Schematic summary of the known effects of androgens and estrogens in the developing hippocampus during the critical period of sexual differentiation in rodents. The perinatal rise in circulating fetal testosterone in males provides substrate for the synthesis of dihydroxytestosterone (DHT) and estradiol in neural cells through the activity of 5-alpha reductase and aromatase, respectively. Neurosteroids are also synthesized de novo in the developing hippocampus of males and females. Androgen-specific and estradiol-specific effects of steroid hormones are found in the developing hippocampus which are most proximally represented by modulation of the cellular response to neurotransmitters. More persistent changes in the cytoarchitecture of the hippocampus are also programmed by neonatal steroids, including alterations in cell genesis, neuronal maturation, and spine synapse density. Ultimately these changes are associated with differences in hippocampal function in adults