Progesterone reduces pentylenetetrazol-induced ictal activity of wild-type mice but not those deficient in type I 5α-reductase

Purpose: To investigate the importance of progesterone (P-4) metabolism by the 5alpha-reductase type I enzyme in mitigating P-4 antiseizure effects. Methods: Ovariectomized, female homozygous and heterozygous 5alpha-reductase type I knockout mice (n = 23) and their wild-type siblings (n = 31) were administered P-4 (1.0 mg), and their pentylenetetrazol (PTZ)-induced ictal behaviors were compared with those of vehicle-administered mice (n = 49). Results: Mice deficient in the 5alpha-reductase type I enzyme administered P-4, or vehicle-administered control mice, had significantly shorter latencies and increased incidence of PTZ-induced hindlimb extension and death than did wild-type mice administered P-4. Conclusions: These data suggest that P-4's metabolism by the 5alpha-reductase type I enzyme may mitigate some of P-4's antiseizure effects in the PTZ-induced seizure model.