This application proposes to characteize RNA and protein metabolism in the hippocampus in response to corticosterone (CS). Incubation of hippocampal slices from adrenalectomized (ADX) rats with CS leads to a 25% increase in labeling of nuclear RNA from 3H-uridine and a 74% increase in labeling of the nuclear poly(A)-containing RNA. Incubation of slices with progesterone is without effect. Further characterization will determine the regional specificity of the effect, the dose-response curve for CS and other steroids, the effect of CS-replacement treatment and the location of the increased labeling in either neurons or glia. The size of the effect on nuclear poly(A)-containing RNA, a premessenger RNA fraction, suggests that comparison of hippocampal cytoplasmic mRNA fractions, from control, as compared to ADX, rats may demonstrate steroid-determined proteins. Hippocampal mRNA fractions will be translated in both the wheat germ and reticulocyte lysate systems. A double-label (3H/35S methionine) protocol will be combined with one and two dimensional gel electrophoresis following incubation of hippocampal slices with or without CS to identify steroid-determined proteins. For both the RNA and protein metabolism studies, labeling of the precursor pools in control and steroid-containing incubations will be assessed. Synaptic plasma membrane (SPM) proteins from the hippocampus of intact, sham-operated and ADX rats have been compared. No alteration in the protein staining pattern is seen, but adrenalectomy causes inhibition of SPM protein phosphorylation in the hippocampus. This effect is due to a transient decrease in hippocampal ACTH content following adrenalectomy. Interaction of other peptides (somatostatin, VIP) with hippocampal SPM protein phosphorylation will be analyzed. Similar analyses will be extended to hippocampal cytosolic fractions to identify steroid-determined alterations in protein phosphorylation. This study is intended to characterize neurochemical events in the hippocampus which might correlate with extensive studies carried out using the hippocampal slice preparation as a model of neuronal plasticity. Results derived from these studies might have relevance to clinical and pharmaceutical approaches to longterm stress, aging, learning disabilities, and in consideration of hormonal therapies and their side affects in the CNS.