Nerve growth factor induces elevation of steroid 5alpha-reductase mRNA levels in rat C6 glioma cells through expression of transcription factor Egr-1.
Steroid 5alpha-reductase type 1 (5alpha-R), the enzyme converting progesterone and other steroid hormones to their 5alpha-reduced metabolites, has been shown to be localized in both neuronal and glial cells, and this enzyme in glial cells has previously been reported to be activated either by co-culturing with neuronal cells or by adding the conditioned medium of neuronal cells, thus suggesting that neuronal activity may be implicated in the regulation of neurosteroid metabolism in brain. In the present study, to investigate a potential role of neurotrophic factors in the mechanism regulating the production of neuroactive 5alpha-reduced steroid metabolites, the direct action of NGF on 5alpha-R gene expression was examined by measuring the steady-state levels of 5alpha-R mRNA levels in rat C6 glioma cells. Exposure of the glioma cells to NGF increased both 5alpha-R mRNA and its protein levels, and induced the transient elevation of Egr-1 mRNA levels prior to the expression of 5alpha-R mRNA in the cells. Furthermore, NGF failed to induce any significant elevation of 5alpha-R mRNA levels in the cells pretreated with Egr-1 antisense oligodeoxynucleotides. These findings indicate that NGF induces the elevation of 5alpha-R gene expression in the glioma cells through the expression of transcription factor Egr-1, proposing the possibility that NGF, and probably other neurotrophic factors as well, may play a potential role in the regulation of 5alpha-reduced steroid production as one of the factors mediating the intercellular communication between neuronal and glial cells in the brain.
Her
Song
S
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5485, USA.
Arimochi
Hideki
H
Morita
Kyoji
K
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020932:Nerve Growth Factor / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase