Attenuating 5α-Pregnane-3α-Ol-20-One Formation in the Hippocampus of Female Rats Increases Pentylenetetrazole-Induced Seizures

The study investigated the role of the 5α-reduced metabolite of progesterone, 5α-pregnan-3α-ol-20-one (3α,5α-THP), in the hippocampus for its antiseizure effects in female rats. In two experiments involving ovariectomized rats, it was found that administration of progesterone increased seizure latency and decreased seizure frequency, correlating with increased hippocampal 3α,5α-THP levels. However, when finasteride, a 5α-reductase inhibitor, was administered, it attenuated the antiseizure effects of progesterone and reduced 3α,5α-THP levels. Finasteride alone did not affect seizure activity or 3α,5α-THP levels. These findings suggested that the formation of 3α,5α-THP in the hippocampus was crucial for the antiseizure effects of progesterone.