Aromatase Promoter I.f is Regulated by Estrogen Receptor Alpha (ESR1) in Mouse Hypothalamic Neuronal Cell Lines

Aromatase (CYP19A1) catalyzes the conversion of C19 steroids to estrogens. Aromatase and its product estradiol (E2) are crucial for the sexually dimorphic development of the fetal brain and the regulation of gonadotropin secretion and sexual interest in adults. The regulation of aromatase expression in the brain is not well understood. The aromatase (Cyp19a1) gene is selectively expressed in distinct neurons of the hypothalamus through a distal brain-specific promoter I.f located ∼36 kb upstream of the coding region. Here, we investigated a short feedback effect of E2 on aromatase mRNA expression and enzyme activity using estrogen receptor alpha (ESR1; also known as ERalpha)-positive or ESR1-negative mouse embryonic hypothalamic neuronal cell lines that express aromatase via promoter I.f. Estradiol regulated aromatase mRNA expression and enzyme activity in a time- and dose-dependent manner, whereas an E2 antagonist reversed these effects. The nucleotide −200/−1 region of promoter I.f conferred E2 responsi...