Pregnancy Terminating Effect of a Highly Active LH-RH Agonist by Vaginal Application in Rats

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A potent LH-RH agonist, des-Gly<SUP>10</SUP>-[D-Leu<SUP>6</SUP>]-LH-RH-ethylamide (TAP-144), administered to pregnant rats by the intravaginal and subcutaneous routes terminated pregnancy most effectively during days 7-11 of pregnancy. A daily administration of TAP-144 during days 7-10 was more effective by the intravaginal than by the subcutaneous route. When TAP-144 was administered twice a day during this period for one to three days, the effective dose became almost the same in the two routes. Complete termination of pregnancy occurred following a dose of 1μg/ 100 g body weight/a time by a single-day administration and 0.01μg/100 g body weight/a time by three days administrations. Previously we found that the serum concentration of TAP-144 after vaginal administration was lower but much longer-sustained than that after subcutaneous administration. Thus, in pregnancy termination, the prolonged duration of an effective concentration of TAP-144 seems to be more important than a transient high concentration. When rats were given effective doses of TAP-144 twice a day on day 9 by either route, ovulation occurred the next day (day 10) and the fetuses were aborted on day 11. Serum concentrations of progesterone and estradiol-17β dropped sharply. Estrus occurred on days 11-13, cycles were established thereafter, and ovulation occurred at regular intervals.
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