Control of masculinization of the brain and behavior

Abstract

Sex steroid hormones exert a profound influence on the sexual differentiation and function of the neural circuits that mediate dimorphic behaviors. Both estrogen and testosterone are essential for male typical behaviors in many species. Recent studies with genetically modified mice provide important new insights into the logic whereby these two hormones coordinate the display of sexually dimorphic behaviors: estrogen sets up the masculine repertoire of sexual and territorial behaviors and testosterone controls the extent of these male displays.

Figure 1. Neural pathways underlying sexually dimorphic behaviors

Many hypothalamic and amygdalar centers have been implicated in the control of sex specific behaviors. Each of these brain regions is sexually dimorphic and expresses one or more gonadal hormone receptors [37,38]; in addition, the BNST, MeA, POA, and VMH also express aromatase [18**], and represent sites of estrogen synthesis in the adult brain. Some of these nuclei and their connections, including with pheromone sensing neurons in the MOE and VNO, are illustrated in this schematic [31,32,54,70,71]. AOB, accessory olfactory bulb; BNST, bed nucleus of the stria terminalis; MeA, medial amygdala; MOB, main olfactory bulb; PLCO, posterolateral cortical amygdala; PMV, ventral premamillary nucleus; POA, preoptic hypothalamus; VMH, ventromedial nucleus of the hypothalamus.

Figure 2. Model for the control of male typical sexual and territorial behaviors

(A) Schematic illustrating that masculinization of the neural substrates for mating and territorial behaviors, including the expression of aromatase and AR [18**,43**], proceeds largely under the control of estrogen, which is synthesized in the brain from circulating testosterone via the action of aromatase. Both estrogen and testosterone, signaling via their cognate receptors, act on this masculinized substrate to activate male pattern behaviors. (B) Genetic inactivation of odor evoked activity in the MOE or VNO shows that both chemosensory pathways control male mating and aggression [–56]. The MOE and VNO are essential for male aggression in a non-redundant manner. The MOE is essential for male sexual behavior, whereas the VNO appears to inhibit it. MOE signaling in conjunction with the high titer of testosterone increases the frequency of male courtship towards females, whereas females, who have low titers of this hormone, exhibit male type mating towards other females at a reduced frequency. The same repertoire of pheromonal receptors appears to be expressed in the two sexes, indicating that males and females can sense male pheromones, which inhibit male type mating in both sexes and promote aggression in males. This suggests that the central pathways that process pheromonal or hormonal cues for male typical fighting may be sexually dimorphic.