Oestrogen receptor alpha is essential for female-directed chemo-investigatory behaviour but is not required for the pheromone-induced luteinizing hormone surge in male mice.

The expression of normal masculine sexual behaviour requires testosterone. Testosterone can bind to androgen receptors, either in its native form, or after reduction to other androgen metabolites. In addition, testosterone can be aromatized to oestrogen, and bind to oestrogen receptor alpha and/or beta. Male copulatory behaviour is deficient in mice lacking functional oestrogen receptor alpha gene (ERalphaKO mice). We sought to determine which aspect(s) of masculine sexual behaviour is compromised in the ERalphaKOs. Specifically, we asked whether ERalphaKO males have reduced motivation and/or an inability to recognize oestrous females. We found significant differences between mice of different genotypes in the amount of chemo-investigatory behaviour displayed and in the target of their investigation. Wild-type males spent more time investigating ovariectomized, oestradiol-treated females, than either males, or ovariectomized females that had not received hormone priming. ERalphaKO males spent little time investigating any of the stimulus mice and showed no preferences. To test the hypothesis that this lack of chemo-investigatory behaviour is due to the inability of ERalphaKO males to detect and respond to female pheromones, we exposed males to chemosensory cues (soiled bedding) from females. Males resided in clean, or female-soiled, cage bedding for 60 min. Next, blood was collected and plasma luteinizing hormone (LH) assayed. We also assessed Fos-like immunoreactivity (Fos-ir) in several neural regions involved in processing chemosensory cues. Despite the fact that male ERalphaKOs spend little time engaged in chemo-investigation of females, their neuroendocrine responses to female-soiled bedding were similar to those seen in wild-type males. Our data suggest that the normal coupling between the neuroendocrine response to females and the generation of sexual behaviour is disrupted in ERalphaKO mice. Responses to female pheromones do not require ERalpha. However, normal male sexual performance requires the ERalpha gene.