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

Abstract

Purpose: To investigate the importance of progesterone (P4) metabolism by the 5α-reductase type I enzyme in mitigating P4 antiseizure effects. Methods: Ovariectomized, female homozygous and heterozygous 5α-reductase type I knockout mice (n= 23) and their wild-type siblings (n= 31) were administered P4 (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 5α-reductase type I enzyme administered P4, 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 P4. Conclusions: These data suggest that P4's metabolism by the 5α-reductase type I enzyme may mitigate some of P4's antiseizure effects in the PTZ-induced seizure model.