title: Endocrine features of glucocorticoid endangerment in hippocampal astrocytes.
abstract: Metabolic insults, such as ischemia or hypoglycemia, typically cause severe neuronal injury in the hippocampus and this cell vulnerability can be exacerbated by glucocorticoid (GC) exposure. This endangerment can also be demonstrated in vitro in both neurons and astrocytes. Direct GC effects on cell physiology thus appear to play a role, but the actual mechanism remains unclear. In order to clarify whether GCs act as damaging agents via a 'classical' steroid route, we examined the temporal features and steroid-specificity of this synergy in hippocampal astrocyte cultures derived from E18 fetal rats. A 24-hour pretreatment with corticosterone (CORT), the principal GC in the rat, enhanced both hypoxic and hypoglycemic cell damage, as measured by lactate dehydrogenase assay. This damaging effect was abolished when CORT exposure was reduced to 8 or 4 h prior to the hypoglycemic or hypoxic treatment, respectively. A 24-hour exposure to several nonGC steroids also failed to enhance hypoxic cell damage. The damaging effect of CORT was attenuated if steroid exposure occurred during the hypoglycemic insult and was absent in both hypoxic and hypoglycemic paradigms if CORT exposure was limited to the recovery period. These results suggest that GCs aggravate metabolic astrocyte injury via classical hormonal effects that are steroid-specific, receptor-mediated, and emerge slowly after prolonged steroid exposure.
authors: Department of Biological Sciences, Stanford University, Calif.
authors: G C
authors: GC
authors: Tombaugh
authors: R M
authors: RM
authors: Sapolsky
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D003345:Corticosterone / Q000633:toxicity*; D005947:Glucose / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007003:Hypoglycemia / Q000473:pathology; D002534:Hypoxia, Brain / Q000473:pathology; D051381:Rats
chemical_list: D005947:Glucose; D003345:Corticosterone