Estrogen receptor alpha knockout (ERaKO) male mice fail to display sexual behavior. The authors hypothesized that ERalphaKOs require higher testosterone (T) concentrations than wild-type (WT) males to exhibit copulatory behavior. Increasing T stimulated sexual behavior and preference for females in WT males but failed to do so in ERalphaKOs. However, T did induce female-directed aggression in ERaKOs. In aggression tests, WT residents selectively attacked T-treated male intruders. ERaKO residents attacked female, T-treated male, and estrogen-treated male intruders equally. Increased access to olfactory cues prior to direct contact reduced overall aggression in ERalphaKO versus WT males but did not cause ERalphaKOs to differentially attack male and female opponents. Results suggest that ERalpha is essential for normal social behavior, perhaps via processing of chemoinvestigatory cues, which are required to discriminate males from females.
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