Identification of estrogen target genes in human neural cells

In mammals, estrogens have a multiplicity of effects ranging from control o f differentiation of selected brain nuclei, reproductive functions, sexual behavior. In addition, these hormones influence the manifestation of disord ers like depression and Alzheimer's. Study of the cells target for the horm one has shown that estrogen receptors (ERs) are expressed in all known neur al cells, including microglia. In view of the potential interest in the use of estrogens in the therapy of several pathologies of the nervous system, it would be of interest to fully understand the mechanism of estrogen activ ity in the various neural target cells and get an insight on the molecular means allowing the hormone to display such a variety of effects. We have pr oposed the use of a reductionist approach for the systematic understanding of the estrogen activities in each specific type of target cell. Thus, we h ave generated a model system in which to study the activation of one of the known (ERs), estrogen receptor alpha. This system allowed us to identify a number of novel genes which expression may be influenced following the act ivation of this receptor subtype by estradiol (E-2). We here report on data recently obtained by the study of one of these target genes, nip2, which e ncodes a proapoptotic protein product. We hypothesize that nip2 might be an important molecular determinant for estrogen anti-apoptotic activity in ce lls of neural origin and represents a potential target for drugs aimed at m imicking the E-2 beneficial effects in neural cells. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.