Estrogen can be proconvulsant, while
progesterone and its metabolite
allopregnanolone typically have anti-seizure effects. We investigated whether
estrogen-priming also has anti-seizure effects by altering
progesterone's metabolism to
allopregnanolone, or levels of
brain-derived neurotrophic factor (
BDNF), in the hippocampus. Two experiments investigated effects of different
estrogen-priming regimen (Experiment 1--10 microg; Experiment 2--2 microg) on
pentylenetetrazole (PTZ)-induced
seizures and levels of
estrogen,
progesterone and
allopregnanolone in plasma and hippocampus. In Experiment 1, ovariectomized (ovx) rats were administered
sesame oil vehicle or 10 microg 17beta-estrogen at hour 0. Forty-four hours later,
progesterone (500 microg; s.c.) or vehicle was administered. At hour 47, PTZ (70 mg/kg i.p.) was administered. For Experiment 2, a similar protocol was used except that ovx rats were administered vehicle or 2 microg 17beta-estradiol at hours 0 and 24.
Progesterone, alone or in conjunction with either 10 or 2 microg
estrogen-priming, tended to increase the latency to, and significantly reduced the number of,
tonic seizures and elevated levels of
progestins in hippocampus and plasma. Two, but not 10, micrograms of
estrogen alone had anti-seizure effects and increased levels of
allopregnanolone in the hippocampus.
BDNF levels in the hippocampus were increased by
estrogen-priming, but reduced by
progesterone administration. Thus,
estrogen may have anti-seizure effects by enhancing formation of
allopregnanolone.