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The role of aromatase in sexually dimorphic behaviors


All sexually reproducing animals display sex differences in social behaviors. These dimorphic behaviors are a consequence of molecular, cellular and circuit-level sex differences in the brain. In mice, these differences arise as a result of masculinization (or not) during the perinatal critical period. My lab has shown explicitly that perinatal exposure to estrogen is the key to masculinization of the brain. A male-specific surge of testosterone is then converted to estrogen by the enzyme aromatase, which is expressed locally in the brain. Estrogen then initiates a cascade of events that permanently alter the brain and prime it for male-typical behaviors. Females, in contrast, have no perinatal sex hormone surge. Estrogen, however, also acts in the adult brain, in both males and females, though its actions have not yet been delineated. My thesis addresses both the developmental and adult roles for estrogen and aromatase, as well as the neurons within the brain that express aromatase. I first examine the role of aromatase in the process of feminization of the brain. I find that absence of aromatase is both necessary and sufficient to produce a feminized brain and that feminization does appear to be the default state of the brain. I then examine the role of estrogen in adulthood and show that loss of aromatase function in males has no behavioral consequences for any of the behaviors I assayed. Because aromatase appears to be playing a minimal role in adulthood, its continued expression within the adult brain remains a mystery. I next explored the role of the neurons expressing aromatase, specifically within the medial amygdala (MeA), because the MeA has been shown to be important for sex-specific behaviors. Using an aromatase-Cre mouse, I show that ablation or inactivation of aromatase-expressing neurons in the MeA results in a mild deficit in aggression, but has no effect on mating behavior. All together, my findings show that presence or absence of aromatase dictates masculinization or feminization of the brain, and in adulthood, marks neurons within the brain that are necessary for sex-specific behaviors.

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