RAPID INCREASE IN GLYCEROL PHOSPHATE DEHYDROGENASE MESSENGER-RNA IN ADULT-RAT BRAIN - A GLUCOCORTICOID-DEPENDENT STRESS-RESPONSE

Twenty-five years ago, glycerol phosphate dehydrogenase (GPDH, EC 1.1. 1.8) was described as a hormonally dependent enzyme in the brain, and since then has been characterized for its developmental regulation and as a marker for oligodendrocytes. These studies describe the cloning of GPDH mRNA from adult rat hippocampus and its characterization as an in vivo response in the brain to both glucocorticoid treatment and st ress. A nearly full-length cDNA clone was obtained with sequence homol ogy to the adult mouse GPDH gene. Three EcoRI fragments derived from t his clone each hybridized to a major 2.9-kb transcript in poly(A)-cont aining RNA. GPDH mRNA increased up to 10-fold in a dose-dependent mann er in response to acute corticosterone (CORT) treatment (8 h-3 days) o f adrenalectomized (ADX) rats. Hybrid-selected GPDH mRNA encodes a 35- kD, pI 6.3 polypeptide that comigrated with our previously described C ORT-responsive 35-kD in vitro translation product, with which it share s the same response characteristics. The basal (morning) AM prevalence of GPDH mRNA in the hippocampus is approximately 0.5 pg/mu g total RN A. Shaking stress increased GPDH mRNA 4-fold; this increase was comple tely blocked by prior ADX. Hippocampal GPDH mRNA prevalence in ADX rat s did not differ from AM intact rats, but increased to stress levels w ithin 2 h of a CORT treatment that produced serum levels in the high p hysiological or stress range. GPDH expression increased throughout the brain of CORT-treated compared with ADX rats by in situ hybridization ; the pattern of expression is similar to that of proteolipid protein mRNA and is consistent with a predominant expression in oligodendrocyt es in white matter. Restraint and cold stress also increased GPDH mRNA in the brainstem. These results establish GPDH mRNA as a glucocortico id-dependent stress response in adult rat hippocampus and indicate tha t glucocorticoid regulation of GPDH enzyme activity throughout the bra in could result from changes in GPDH mRNA prevalence. In addition to i ts role in development, GPDH may participate in oligodendrocyte respon ses to stress in the adult brain.