Differential expression of the estrogen receptors alpha and beta during postnatal development of the rat cerebellum.

Estrogen receptor (ER) beta is a dominant ER subtype in the adult cerebellum. However, it is not known if this is also the case for the developing cerebellum. In the present study, quantitative real-time RT-PCR demonstrated that levels of cerebellar ERalpha mRNA in neonatal pups were significantly higher than in adults. In contrast, expression levels of cerebellar ERbeta mRNA remained significantly unchanged during postnatal development. In situ hybridization and immunohistochemistry demonstrated that ERalpha mRNA and protein were predominantly expressed by Purkinje cells at all ages examined. ERalpha-expressing Purkinje cells were confined to the anterior lobes at postnatal day 7 (P7) but distributed in most lobes at P14 and P21. In the adult cerebellum, however, only a few ERalpha-immunoreactive Purkinje cells were observed. Thus, ERalpha expression was transiently increased during the time when Purkinje cell dendritic growth and synapse formation proceed, suggesting that a role for ERalpha in Purkinje cell differentiation. ERbeta expression occurred in Golgi type neurons in the granular layer at P7, Purkinje cells at P14, and basket cells in the molecular layer at P21 and was detected in all the cell types in the adult cerebellum, suggesting a role for ERbeta associated with neuronal differentiation and maintenance. Furthermore, double-labeled immunofluorescence for ERalpha and ERbeta demonstrated their colocalization in Purkinje cells at P14, suggesting a possibility of their interaction. The discrete expression profiles for ERalpha and ERbeta in the developing cerebellum suggest the two ERs play distinct roles in cerebellar development.