OBJECTIVES: Local estrogen production in the brain regulates critical functions including neuronal development, gonadotropin secretion and sexual behavior. In the mouse brain, a 36 kb distal promoter (l.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for estrogen biosynthesis. In vitro, promoter l.f interacts with estrogen receptor alpha (Esr1) to mediate Cyp19a1 mRNA expression and enzyme activity in mouse hypothalamic neuronal cell lines. The in vivo mechanisms that control mammalian brain aromatase expression during fetal and adult development, however, are not thoroughly understood. Our aim was to elucidate the basis of the in vivo connection between Esr1 and Cyp19a1.
METHODS: Pregnant mice were sacrificed at gestational days 9, 11, 13, 15, 16, 19, 21 and the brain tissues of the fetuses were harvested along with five newborns at the age of postnatal day 2. Esr1KO (female) were also sacrificed and their hypothalamus were excised out. Then both fetuses and adults RNA were isolated, reverse transcribed and amplified employing primers specific for Esr1 and Cyp19a1 with Real time PCR.
RESULTS: In the fetal mouse brain, Cyp19a1 mRNA levels are inversely correlated with estrogen receptor alpha (Esr1) mRNA levels in a temporal manner. Moreover, Cyp19a1 mRNA levels increased in the hypothalamus of estrogen receptor-alpha knockout female mice (Esr1KO).
CONCLUSION: Taken together, our findings might indicate that Esr1 has crucial roles in the in vivo regulation of aromatase expression in the brain during fetal and adult life....