Transcriptional analysis of estrogen effects in human embryonic neurons and glial cells

Estrogen exerts many effects in the central nervous system which extend beyond regulating sexual behavior and gonadal function in reproduction. It has been shown that estrogen has a range of both neuroprotective and neuromodulatory effects, but little is known about the molecular mechanisms underlying estrogen actions in the human brain. We therefore analyzed the transcriptional response to estrogen by microarray technology in primary cell cultures of neurons and glial cells derived from 8- to 12-week human fetal brain tissue. Estrogen treatment of the cell cultures during a 7-day culture period revealed a number of genes with significantly altered expression. Fourteen genes were selected for further analysis by quantitative real-time PCR in order to confirm the gene expression changes observed by the microarray analysis. Six genes were identified with important roles in the nervous system that have not been described before to be estrogen-regulated. Three genes, IGFBP7, Transgelin and Cyr61, were further analyzed by immunostaining, and were found to be expressed in both primary neurons and glial cells. Our results indicate that estrogen may influence developing human neurons and glia through regulating expression of genes that are important for the development of the nervous system.