Men and women suffer disproportionally from specific neurological and psychiatric disorders and the basis for this difference remains unclear. However, given that males and females are exposed to different levels of steroids throughout development, a role for these hormones in the etiology of sexually dimorphic neurological disorders is strongly suggested. Investigating the consequences of this dimorphic exposure will help elucidate the mechanisms of steroid action on the developing brain. Previous research in our laboratory implicates astrocytes as an important target of steroid hormone action in select regions of the developing perinatal rodent brain. The preoptic area (POA) is a major brain region controlling sex-typic behavior and physiology, and preliminary data suggest that astrocytes of this region are also responsive to steroids. We have found that as early as the day of birth, the morphology of astrocytes of the POA are sexually dimorphic. The importance of astrocytes in the establishment of neuronal architecture is becoming increasingly evident. The goal of this proposal is to elucidate the mechanism(s) of steroid-mediated changes in POA neuronal morphology involving neighboring steroid-sensitive astrocytes. Hormonal manipulation experiments will establish the steroid specificity determining neuron differentiation within the developing POA. To begin to determine the functional relationship between the two cell types, experiments will identify the components of an astrocyte-to-neuron communication cascade and examine the effect of steroid manipulation on this system. Pharmacological manipulations and the use of antisense oligodeoxynucleotides will explore the roles of prostaglandin E2 and the activation of their cognate receptors in this signal transduction mechanism.
