Pregnancy terminating effect of a highly active LH-RH agonist by vaginal application in rats.
A potent LH-RH agonist, des-Gly10-[D-Leu6]-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 1 microgram/100 g body weight/a time by a single-day administration and 0.01 microgram/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-17 beta dropped sharply. Estrus occurred on days 11-13, cycles were established thereafter, and ovulation occurred at regular intervals.
D000021:Abortifacient Agents, Steroidal / Q000008:administration & dosage; D000028:Abortion, Induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D004971:Estrus; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007279:Injections, Subcutaneous; D016729:Leuprolide; D010060:Ovulation; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D051381:Rats; D013997:Time Factors; D014621:Vagina
D000021:Abortifacient Agents, Steroidal; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D016729:Leuprolide