Phenytoin inhibits both the first ovulation and uterine development in gonadotropin-primed immature rats

This study was planned to determine the effects and possible mechanism of a ction of phenytoin on development of the reproductive tract and first ovula tion in immature rats. Rats were injected s.c, with 5 IU of equine chorioni c gonadotrophin (equine CG) on day 26 to induce ovarian and uterine develop ment. Treatment with phenytoin (140 mg/kg) at 1200 h on day 28, which induc es serum levels approximately twice those reached with the clinical dose as anticorvulsant drug for humans, was effective for inhibiting the first ovu lation and normal secretion of serum follicle - stimulating hormone and lut einizing hormone (LH) on day 29 as well as the preovulatory gonadotrophin s urge on day 28. The block of ovulation was overcome by administration of hu man chorionic gonadotrophin or LH-releasing hormone on day 28. Simultaneous treatment with equine CG and phenytoin at 0800 h on day 26 did not affect either ovarian weight or ovarian hormones secretion, whereas phenytoin clea rly inhibited the normal increase in uterine weight on day 27. Furthermore, phenytoin suppressed uterine growth after 17 beta-oestradiol injection. Th ese results indicate that phenytoin inhibits the first ovulation by inhibit ing the gonadotrophin surge and further, that the drug impairs the stimulat ory effects of oestrogen on uterine proliferation in the gonadotropin-induc ed ovulation model. (C) 2000 Elsevier Science B.V. All rights reserved.