Progesterone reduces pentylenetetrazol-induced ictal activity of wild-type mice but not those deficient in type I 5alpha-reductase.
OBJECTIVE
To investigate the importance of progesterone (P4) metabolism by the 5alpha-reductase type I enzyme in mitigating P4 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 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 5alpha-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 5alpha-reductase type I enzyme may mitigate some of P4's antiseizure effects in the PTZ-induced seizure model.
Frye
Cheryl A
CA
Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@cnsunix.albany.edu
Rhodes
Madeline E
ME
Walf
Alicia
A
Harney
Jacob
J
D000818:Animals; D003292:Convulsants; D005260:Female; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010088:Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D010433:Pentylenetetrazole; D011374:Progesterone / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology*
D003292:Convulsants; D011374:Progesterone; D010088:Oxidoreductases; C022447:3-oxo-5-alpha-steroid 4-dehydrogenase (NADP(+)); D010433:Pentylenetetrazole