Background: Local oestrogen production in the brain regulates critical functions including neuronal development, gonadotropin secretion and sexual behaviour. In the mouse brain, a 36 kb distal promoter (l.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for oestrogen biosynthesis. In vitro, promoter l.f interacts with oestrogen receptor alpha (Esr1) and Progesterone receptor (Pgr) 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.
Objective and hypotheses: Our aim was to elucidate the basis of the in vivo connection between Esr1, Pgr and Cyp19a1.
Method: Pregnant mice were sacrificed at gestational days 9, 11, 13, 15, 16, 19, 21 and the brain tissues of the foetuses 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 foetuses and adults RNA were isolated, reverse transcribed and amplified employing primers specific for Esr1, Pgr and Cyp19a1 with Real time PCR.
Results: In the foetal mouse brain, Cyp19a1 mRNA levels are inversely correlated with both Esr1 and Pgr mRNA levels in a temporal manner. Moreover, Cyp19a1 mRNA levels increased in the hypothalamus of oestrogen receptor-alpha knockout female mice (Esr1KO).
Conclusion: Taken together, our findings might indicate that Esr1 and Pgr have crucial roles in the in vivo regulation of aromatase expression in the brain during foetal and adult life.
Funding information: Northwestern University start up funds.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology