title: CYP19 expression is induced by 2,3,7,8-tetrachloro-dibenzo-para-dioxin in human glioma cells.
abstract: Dioxins are the most concerned environmental pollutants. Recent studies have shown that these compounds could disrupt the proper functioning of our endocrine system. Estrogen is synthesized in glial cells of the brain. The hormone has been linked to the maintenance of normal brain operation, ranging from neurotransmission to synapse formation. Aromatase or CYP19 is the enzyme responsible for estrogen synthesis. In the present study, we demonstrated that 2,3,7,8-tetrachloro-dibenzo-para-dioxin (TCDD) stimulated the enzyme activity in human brain cells as low as 1pM. Increased brain-specific CYP19 mRNA species was also observed in these cells. Since the brain-specific promoter I.f of CYP19 contains two binding motifs for CCAAT/enhancer binding protein, electrophoretic mobility shift assay was performed to validate the activation. We further traced the triggering signal and found that the mitogen-activated protein kinases ERK-1/2 were activated. In summary, TCDD could induce CYP19 transcription in brain cells. Exposure to the pollutant might perturb the hormonal balance in the brain.
authors.affiliation: Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Tan
authors.forename: Tsz Yan
authors.initials: TY
authors.lastname: Wong
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004785:Environmental Pollutants / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005910:Glioma; D006801:Humans; D020935:MAP Kinase Signaling System; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology; D009570:Nitriles / Q000494:pharmacology; D009928:Organ Specificity; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding
chemical_list: D002070:Butadienes; D022762:CCAAT-Enhancer-Binding Proteins; D004785:Environmental Pollutants; D009570:Nitriles; D000072317:Polychlorinated Dibenzodioxins; C113580:U 0126; D001141:Aromatase; D048049:Extracellular Signal-Regulated MAP Kinases