During neonatal development glucocorticoids potentiate oligodendrocyte differentiation and myelinogenesis by regulating the expes of myelin basic protein, proteolipid protein, and glycerol phosphate dehydrogenase (snglycerol-3-phosphate: NAD' 2-oxidoreductase, EC 1.1.1.8).The actual locus at which hydrocortisone exerts its developmental influence on glal physiology is, however, not well understood. Gycerol phosphate dehydrogenase is glucocorticoid-inducible in oligodendrocytes at all stages of development both in vivo and in vitro. In newborn rat cerebral cultures, between 9 and 15 days in vitro, a 2-to 3-fold increase in myelin basic protein and proteolipid protein mRNA levels occurs in oligodendrocytes within 12 hr of hydrocortisone treatment. Immunotaining demonstrates that this increase in mRNAs is followed by a 2-to 3-fold increase in the protein levels within 24 hr. In vitro transcription assays performed with oligodendrocyte nuclei show an 11-fold increase in the transcriptional activity of glycerol phosphate dehydrogenase in response to hydrocortisone but no increase in transcription of myelin basic protein or proteolipid protein. These results indicate that during early myelinogenesis, glucocorticoids influence the expression of key oligodendroglial markers by different processes: The expression of glycerol phosphate dehydrogenase is regulated at the transcriptional level, whereas the expression of myelin basic protein and proteolipid protein is modulated via a different, yet uncharacterized, mechanism involving posttranscriptional regulation.The expression of glycerol phosphate dehydrogenase (GPDH; sn-glycerol-3-phosphate: NAD' 2-oxidoreductase, EC 1.1.1.8), myelin basic protein (MBP), and proteolipid protein (PLP) marks the differentiation of oligodendrocytes, the myelinating cells in the central nervous system (1, 2). MBP and PLP are components of the myelin sheath, constituting 30%o and 50%o of the proteins in myelin, respectively. The expression and biosynthesis of MBP and PLP in oligodendrocytes have been shown to be coordinately expressed with the process of myelination (3)(4)(5)(6).Peak expression of GPDH during neonatal development also coincides with the active period of myelination (7,8). Localized in oligodendrocytes (9), GPDH provides glycerol phosphate for the biosynthesis of phosphatides (10), a precursor for membrane components (11). The developmental regulation of GPDH gene expression and its modulation by glucocorticoids in the rat brain and in primary cultures of oligodendrocytes have been well characterized (12).Glucocorticoids and other hormones have been implicated in the stimulation of myelinogenesis (13)(14)(15)(16). During glial differentiation, the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) has been shown to be increased by dexamethasone, a potent glucocorticoid agonist, both in reaggregating (13) and dissociated (14) The ability ofglucocorticoids to influence the developmental expression of genes in the brain correlates highly with the ontogen...