Large-scale identification of proteins involved in the development of a sexually dimorphic behavior.

Sexually dimorphic behaviors develop under the influence of sex steroids, which induce reversible changes in the underlying neural network of the brain. However, little is known about the proteins that mediate these activational effects of sex steroids. Here, we used a proteomics approach for large-scale identification of proteins involved in the development of a sexually dimorphic behavior, the electric organ discharge of brown ghost knifefish, Apteronotus leptorhynchus. In this weakly electric fish, the discharge frequency is controlled by the medullary pacemaker nucleus and is higher in males than in females. After lowering the discharge frequency by chronic administration of β-estradiol, 2-dimensional difference gel electrophoresis revealed 62 proteins spots in tissue samples from the pacemaker nucleus that exhibited significant changes in abundance of >1.5-fold. The 20 identified protein spots indicated, among others, a potential involvement of astrocytes in the establishment of the behavioral dimorphism. Indeed, immunohistochemical analysis demonstrated higher expression of the astrocytic marker protein GFAP and increased gap-junction coupling between astrocytes in females compared with males. We hypothesize that changes in the size of the glial syncytium, glial coupling, and/or number of glia-specific potassium channels lead to alterations in the firing frequency of the pacemaker nucleus via a mechanism mediating the uptake of extracellular potassium ions from the extracellular space.