Estrogen rapidly induces the phosphorylation of the cAMP response element binding protein in rat brain

Estrogen treatment of ovariectomized rats rapidly increases immunoreactivity for the phosphorylated form of the cAMP response element binding protein (CREB) in neurons of the preoptic area and the bed nucleus of the stria terminalis. These effects were detected within 15 min after estrogen exposure. Since the antisera used for these studies detect CREB phosphorylation at ser¹³³, which is important for transcriptional activation, these data provide a possible explanation for estrogen's effects on neuronal genes lacking estrogen response elements (EREs) but which contain cAMP response elements (CREs). These data also provide evidence for non- genomic effects of steroid hormones involving protein kinase associated signal transduction pathways traditionally associated with effects initiated at the cell membrane.