Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain.

ABSTRACT

This study reports on the spatiotemporal dynamics of the expression of estrogen receptors (ERs) in the mouse central nervous system (CNS) during the early postnatal and the peripubertal period. At postnatal day 7 (P7), neurons with strong nuclear immunostaining for both ERalpha and ERbeta1 were widely distributed throughout the brain. Sucrose density gradient sedimentation followed by western blotting supported the histochemical evidence for high levels of both ERs at P7. Over the following 2 days, there was a rapid downregulation of ERs. At P9, ERalpha expression was visible only in the hypothalamic area. Decline in ERbeta1 expression was slower than that of ERalpha, and ERalpha-negative, ERbeta1-positive cells were observed in the dentate gyrus and walls of third ventricle. Between P14 and P35, ERs were undetectable except for the hypothalamic area. As before P7, the ovary does not produce estrogen but does produce 5alpha-androstane-3beta, 17beta-diol (3betaAdiol), an estrogenic metabolite of dihydrotestosterone, we examined the effects of high levels of 3betaAdiol in the postnatal period. We used CYP7B1 knockout mice which cannot hydroxylate and inactivate 3betaAdiol. The brains of these mice are abnormally large with reduced apoptosis. In the early postnatal period, there was 1-week delay in the timing of the reduction in ER expression in the brain. These data reveal that the time when ERs might be activated in the brain is limited to the first 8 postnatal days. In addition, the importance of aromatase has to be reconsidered as the alternative estrogen, 3betaAdiol, is important in neuronal function in the postnatal brain.