The effects of the folic acid antagonist, 4-amino-N10-methylpteroylglutamic acid (methotrexate), and varying doses of folic acid were studied on superovulated immature rats. Methotrexate and folic acid were used alone and in combination with oestrone.The parameters selected for study were organ weights and ovum counts. The administration of methotrexate (200 \g=m\g./rat), folic acid (400 \g=m\g.) or oestrone (500 \g=m\g.)partially inhibited ovulation. When given in combination with oestrone, both methotrexate and folic acid (50\g=m\g.) reversed the fall in ovum counts produced by oestrone.Because either a deficiency or an excess of folic acid partially inhibited ovulation, it is concluded that folic acid plays a significant role in induced ovulation in the immature rat. These effects are probably interrelated with the action of oestrogen.In hypophysectomized immature rats, gonadotrophins increased ovarian and uterine weights when compared with those in untreated hypophysectomized animals, but the simultaneous administration of either methotrexate alone or combined with oestrone prevented these effects. Similar treatment of intact animals showed no differences in ovarian and uterine weights.
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