Anticonvulsant Activity of Progesterone and Neurosteroids in Progesterone Receptor Knockout Mice

The study examined the role of progesterone receptors (PR) in the anticonvulsant effects of progesterone using PR knockout (PRKO) mice. It was discovered that the anticonvulsant potency of progesterone was not reduced in PRKO mice compared to wild-type controls, and in some seizure models, PRKO mice even showed increased potency. The reversal of anticonvulsant effects by finasteride suggested that these effects were due to the conversion of progesterone to the neurosteroid allopregnanolone, rather than the action of PRs. This indicated that PRs were not necessary for the antiseizure effects of progesterone, which were mainly mediated by allopregnanolone.