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Prenatal Testosterone Exposure Influences Neuronal Sensitivity to Pheromones in Female Mice

Roger N Thompson, Audrey Napier and Kennedy S Wekesa

Exposure to androgens during in utero development in animals which give birth to multiple offspring causes lifelong increased sensitivity in the offspring. Females who develop with a male on each side (designated 2M) are exposed to the testosterone produced by these males due to the steroids freely crossing cell membranes. Female mice exposed to testosterone during development are “masculinized” in their growth and behavior. According to the organizational theory, testosterone is converted to estrogen and it is this estrogen which organizes the brain. Increased sensitivity to testosterone is reflected by the exposed females showing increased aggressive behavior and a reduction in production of IP3 levels in the vomeronasal organ (VNO). These 2M females respond more like males when exposed to the pheromonal compounds 2-Heptanone and 2,5-dimethylpyrazine. In previous studies we showed a distinct difference between male and female IP3 production when male and female VNO microvilli are exposed to these compounds. Production of IP3 by male microvilli exposed to 2-Heptanone and 2,5-dimethylpyrazine were the same as the nonstimulus phosphate buffered saline (PBS). In the present study, we provide evidence showing 2M female IP3 production to be similar to that of male mice. In addition, we provide evidence for increased aggression when 2M females are injected with exogenous testosterone.