Sex difference in the brain is a very attractive problem. For example, the hypothalamus, the brain region responsible for reproductive behavior, exhibits a clear sex difference in the size of nerve nucleus.
In contrast, the hippocampus, a center for learning and memory, does not have sex difference at the anatomical level including the volume and the number of neurons. Nevertheless, the significant sex difference in the performance of hippocampus-dependent task such as spatial memory using Morris water maze or radial arm maze task exists.
What generates the sex difference in the performance of learning and memory depending on hippocampus? So far, sex difference in the hippocampus had been attributed to the level of sex hormones in the blood.
However, we revealed that the hippocampal neurons synthesize sex hormones including estradiol (E2), testosterone (T), dihydrotestosterone (DHT) and progesterone (PROG) in both sex. The levels of sex hormones in hippocampus were higher than that in plasma, suggesting that hippocampal sex hormones contribute more to hippocampal functions than circulating ones do. The levels of sex hormones exhibited a clear sex difference, and in female, especially, fluctuated across estrous cycle. Surprisingly, no sex difference in the mRNA level and the localization pattern of steroidogenic enzymes and receptors was observed in the hippocampus.
Moreover, the density of spines (postsynapses) in female hippocampus fluctuated across estrous cycle, whereas that in male retained at a constant level. This cyclic fluctuation of spines in female hippocampus highly correlated with hippocampal level of PROG and E2
This clear sex difference in hormonal profile in hippocampus may generate the sex difference in the hippocampal structure at more subtle level, that is, synaptic level, resulting in the sex difference in the performance of hippocampus-dependent task.