Sex differences in progesterone receptor immunoreactivity in neonatal mouse brain depend on estrogen receptor alpha expression

Around the time of birth, male rats express higher levels of progesterone r eceptors in the medial preoptic nucleus (MPN) than female rats, suggesting that the MPN may be differentially sensitive to maternal hormones in develo ping males and females. Preliminary evidence suggests that this sex differe nce depends on the activation of estrogen receptors around birth. To test w hether estrogen receptor alpha (ER alpha) is involved, we compared progeste rone receptor immunoreactivity (PRir) in the brains of male and female neon atal mice that lacked a functional ERa! gene or were wild type for the disr upted gene. We demonstrate that males express much higher levels of PRir in the MPN and the ventromedial nucleus of the neonatal mouse brain than fema les, and that PRir expression Is dependent on the expression of ER alpha in these regions. In contrast, PRir levels in neocortex are not altered by ER alpha gene disruption. The results of this study suggest that the inductio n of PR via ER alpha may render specific regions of the developing male bra in more sensitive to progesterone than the developing female brain, and may thereby underlie sexual differentiation of these regions. (C) loot John Wi ley & Sons. Inc.