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Because these developmental effects resemble those reported for brain\u2010derived neurotrophic factor (BDNF), we hypothesized that E influences dopaminergic cell differentiation through a BDNF\u2010dependent mechanism. Competitive RT\u2010PCR and ELISA techniques were employed to study first the developmental pattern of BDNF and trkB expression in the mouse midbrain. BDNF protein\/mRNA levels peaked postnatally, whereas trkB did not fluctuate perinatally. To prove the hypothesis that E regulates BDNF expression in vivo, fetuses and newborns were treated with the aromatase antagonist CGS 16949A. CGS 16949A exposure reduced midbrain BDNF mRNA\/protein levels. The coapplication of CGS 16949A and E abolished this effect. Midbrain cultures from mouse fetuses were used to investigate intracellular signaling mechanisms involved in transmitting E effects. Estrogen increased expression of BDNF but not of other neurotrophins. As concerns the related signaling mechanism, these effects were antagonized by interrupting intracellular Ca<jats:sup>2+<\/jats:sup> signaling with BAPTA and thapsigargin but not by the estrogen receptor antagonist ICI 182,780. Insofar as E effects on BDNF mRNA expression were inhibited by cycloheximide, it appears likely that other, not yet characterized intermediate proteins take part in the estrogenic regulation of BDNF expression. We conclude that E exerts its stimulatory effect on the differentiation of dopaminergic neurons by coordinating BDNF expression. This particular E effect appears to be transmitted through Ca<jats:sup>2+<\/jats:sup>\u2010dependent signaling cascades upon activation of putative membrane estrogen receptors. J. Neurosci. Res. 66:221\u2013230, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.1214","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T19:53:55Z","timestamp":1030305235000},"page":"221-230","source":"Crossref","is-referenced-by-count":61,"title":["Estrogen stimulates brain\u2010derived neurotrophic factor expression in embryonic mouse midbrain neurons through a membrane\u2010mediated and calcium\u2010dependent 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