Interplay of hormones and p53 in modulating gender dimorphism of subventricular zone cell number

Previous studies have suggested the existence of a gender bias in repair after demyelination. Here we report the existence of gender dimorphism for the regulation of cell number in the subventricular zone (SVZ), an area that has been studied for its repair potential. The number of Sox2(+) multipotential cells in the SVZ of young adult female mice was greater than in age-matched male siblings, but this difference was not evident prior to the surge of sex hormones (i.e., in prepubertal mice). To begin asking whether hormonally derived signals were responsible for these gender-related differences, we analyzed proliferation and survival of cultured male- and female-derived SVZ cells. Estrogen, but not testosterone treatment increased cell proliferation and survival of cultured cells after IFN-gamma treatment or after UV irradiation, regardless of the gender of origin. Because apoptosis in UV-irradiated SVZ cells correlated with the expression of the proapoptotic molecule p53, we postulated that this molecule could be responsible for the gender dimorphism in the SVZ. In agreement with this prediction, no difference in the SVZ cell number was detected in male and female p53 null mice. Together with previous reports, these results implicate p53 as an important component of the mechanism regulating gender dimorphism in the SVZ.