Adrenergic Activation of Steroid 5α-Reductase Gene Expression in Rat C6 Glioma Cells: Involvement of Cyclic AMP/Protein Kinase A-Mediated Signaling Pathway

• Published in: Journal of molecular neuroscience Vol. 22; no. 3; pp. 205 - 212
• Main Authors: Morita, Kyoji, Arimochi, Hideki, Tsuruo, Yoshihiro
• Format: Journal Article
• Language: English
• Published: 01-01-2004
• ISSN: 0895-8696; 0895-8696
• DOI: 10.1385/JMN:22:3:205

Steroid 5 alpha -reductase (5 alpha -R) is well known as the enzyme converting progesterone and other steroid hormones to their 5 alpha -reduced metabolites and has been reported to be localized in both neuronal and glial cells in the brain. Previously, the enzyme activity in glial cells has been shown to be enhanced either by coculturing with neuronal cells or by adding the conditioned medium of neuronal cells, suggesting a possible implication of neuro-glial interactions in the regulation of neurosteroid metabolism in the brain. In the present studies, the effects of adrenergic agonists on 5 alpha -R mRNA and protein levels in rat C6 glioma cells were examined as one of the model experiments for investigating the influence of neuronal activity on the expression of 5 alpha -R gene in the glial cell. The direct challenge of beta -adrenergic agonists to glioma cells resulted in the rapid and transient elevation of 5 alpha -R mRNA levels through the activation of the cyclic AMP (cAMP)/protein kinase A-mediated signaling pathway. Further studies showed that cAMP-induced 5 alpha -R mRNA expression was completely abolished by pretreatment of cells with actinomycin D and also indicated that the elevation of 5 alpha -R mRNA levels was accompanied by an increase in enzyme protein in the cells. These findings provide strong evidence that the stimulation of beta -adrenergic receptors might induce the transcriptional activation of 5 alpha -R gene expression in glial cells, proposing the possibility that neuronal activity might be involved in the production of neuroactive 5 alpha -reduced steroids in the brain.