CYP19 expression is induced by 2,3,7,8-tetrachloro-dibenzo-para-dioxin in human glioma cells

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 1 pM. 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.