Changes in estrogen receptor-alpha mRNA in the mouse cortex during development

Abstract

Estrogen plays a critical role in brain development and is responsible for generating sex differences in cognition and emotion. Studies in rodent models have shown high levels of estrogen binding in non-reproductive areas of the brain during development, including the cortex and hippocampus, yet binding is diminished in the same areas of the adult brain. These binding studies demonstrated that estrogen receptors decline in the cortex during development but did not identify which of the two estrogen receptors was present. In the current study, we examined the expression of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in the mouse cortex during the first month of life. Messenger RNA was isolated from cortical tissue taken from C57BL/6 mice on postnatal day (PND) 1, 4, 10, 18 and 25 and expression levels were determined by real-time PCR. ERα mRNA expression in the mouse cortex at PND 25 was significantly reduced as compared to PND 1 (p<0.01). ERβ mRNA expression at PND 25 was significantly increased as compared to PND 1 (p<0.05). Although the increase in ERβ mRNA was statistically significant, the ERβ levels were extremely low in the isocortex compared to ERα mRNA levels, suggesting that ERα may play a more critical role in the developmental decrease of estradiol binding than ERβ. Additionally, we measured ERα mRNA expression in organotypic explant cultures of cortex taken from PND 3 mice. Explants were maintained in vitro for 3 weeks. mRNA was isolated at several time points and ERα and ERβ mRNA was measured by real-time RT–PCR. ERα and ERβ mRNA levels reflected a similar pattern in vitro and in vivo, suggesting that signals outside the cortex are not needed for this developmental change. This study lays the groundwork for an understanding of the mechanisms of the developmental regulation of ERα mRNA.