Serotonergic 5-HT2A receptor stimulation induces steroid 5alpha-reductase gene expression in rat C6 glioma cells via transcription factor Egr-1.
Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of depressive mood disorders and well known to inhibit the reuptake of neurotransmitter serotonin into nerve terminals. Thus, it seems conceivable that these drugs may induce the outflow of serotonin from the synapse as a consequence of inhibiting the reuptake, resulting in the stimulation of glial cells surrounding nerve terminals. On this hypothesis, the effect of serotonin on steroid 5alpha-reductase type 1 (5alpha-R) gene expression in rat C6 glioma cells was examined as one of the in vitro model experiments for investigating the indirect influence of SSRIs on glial cells. Serotonin elevated 5alpha-R mRNA and protein levels through the stimulation of serotonin 5-HT2A receptors, and also elevated Egr-1 mRNA and protein levels prior to 5alpha-R gene expression in the glioma cells. Furthermore, serotonin failed to significantly increase 5alpha-R mRNA levels in the cells preloaded with the antisense oligodeoxynucleotide targeted on Egr-1 gene. These results indicate that serotonin may stimulate 5alpha-R gene expression via transcription factor Egr-1 in glial cells, thus suggesting that serotonin flowing out of the serotonergic synapse may be implicated in SSRI-induced changes in neurosteroid metabolism in brain.
Morita
Kyoji
K
Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. km@basic.med.tokushima-u.ac.jp
Arimochi
Hideki
H
Her
Song
S
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005910:Glioma; D009281:Naphthalenes; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D010082:Oxepins; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors
C461941:1-phenyl-1,4-epoxy-1H,4H-naphtho(1,8-de)(1,2)dioxepin; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009281:Naphthalenes; D020320:Oligoribonucleotides, Antisense; D010082:Oxepins; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase