Progesterone attenuates oestrogen neuroprotection via downregulation of oestrogen receptor expression in cultured neurones.

Recent findings indicate that progesterone can attenuate the beneficial neural effects of oestrogen. In the present study, we investigated the hypothesis that progesterone can modulate oestrogen actions by regulating the expression and activity of oestrogen receptors, ERalpha and ERbeta. Our studies in cultured neurones demonstrate that progesterone decreases the expression of both ERalpha and ERbeta and, as a consequence, also reduces both ER-dependent transcriptional activity and neuroprotection. These results identify a potential mechanism by which progesterone antagonises neural oestrogen actions, a finding that may have important implications for hormone therapy in postmenopausal women.