INTERACTIONS OF ESTROGEN WITH THE NEUROTROPHINS AND THEIR RECEPTORS DURING NEURAL DEVELOPMENT

We are interested in examining mechanisms underlying estrogen actions during neuronal differentiation in the central nervous system (CNS). O ur research has focused on one possible mechanism, the developmental i nteractions between estrogen and the neurotrophins (nerve growth facto r [NGF], brain derived neurotrophic factor [BDNF] and neurotrophin-3 [ NT-3]). Using combined isotopic and non-isotopic in situ hybridization , we found that neurons in developmental estrogen targets (e.g., the c erebral cortex), co-localized mRNAs for the neurotrophins (NGF or BDNF ) with their cognate receptors (p75(NGFR) [the pan-neurotrophin recept or] and trkA or trkB [the tyrosine kinase receptors]), suggesting a lo calization of neurotrophin-autocrine loops to these estrogen-sensitive neurons. In contrast, the basal forebrain, which is estrogen-sensitiv e in the adult and during development, only expressed neurotrophin rec eptor mRNAs, suggesting that this region was not an autocrine neurotro phin target. We examined the potential for developmental estrogen-neur otrophin interactions, using a model neurotrophin sensitive system, i. e., differentiating PC12 cells. NGF significantly increased estrogen r eceptor density in PC12 cells. Reciprocally, estrogen up-regulated trk A mRNA and transiently down-regulated p75(NGFR) mRNA, suggesting that estrogen may increase the efficiency of NGF binding in PC12 cells. Sim ilar estrogen-dependent regulation of NGF receptor mRNAs were also obs erved in the adult dorsal root ganglia, suggesting that estrogen may r egulate NGF-sensitivity in adult neurotrophin targets as well. Such es trogen-neurotrophin interactions may have an important role during dif ferentiation and in the adult, following injury, (C) 1994 Academic Pre ss, Inc.