Aggressive interactions rapidly increase androgen synthesis in the brain during the non-breeding season

In male song sparrows (Melospiza melodia), territorial challenges during the breeding season can rapidly increase circulating levels of testosterone (T). During the non-breeding season, male song sparrows are highly aggressive, but the gonads are regressed and plasma T levels are non-detectable and unaffected by territorial challenges. The pro-hormone dehydroepiandrosterone (DHEA) is elevated in song sparrow plasma and brain during the non-breeding season and may be locally converted to sex steroids in the brain to regulate aggression. The enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) converts DHEA to androstenedione (AE) using the cofactor NAD+, and this is a critical rate-limiting step. We predicted that brain 3β-HSD activity varies seasonally and is rapidly modulated by aggressive challenges. In the first study, brain 3β-HSD activity was highest in the non-breeding season in specific regions. In the second study, a simulated territorial challenge rapidly increased aggressive behavior in non-breeding song sparrows. Brain 3β-HSD activity, when measured without exogenous NAD+, increased by ∼ 250 to 500% in telencephalic regions of challenged subjects. When brain 3β-HSD activity was measured with exogenous NAD+, these effects of territorial challenges were not observed. These data suggest that territorial challenges rapidly increase endogenous NAD+ levels or increase 3β-HSD activity specifically within a NAD-rich subcellular compartment. Together, these two studies suggest a shift from systemic to local sex steroid signaling in the non-breeding season. Local steroid signaling produces high spatial and temporal specificity of steroid signals and avoids the costs of high systemic T levels during the non-breeding season.