Blockade of LH Release and Ovulation in the Rabbit with Inhibitory Analogues of Luteinizing Hormone Releasing Hormone1

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Abstract
Plasma LH [luteinizing hormone] levels and ovulation were studied in female rabbits following administration of several inhibitory analogues of luteinizing hormone-releasing hormone (LHRH) before and after mating with experienced males. Administration of (D-Phe2, D-Leu6)-LHRH (1.5 mg/kg s.c.) to doses 30 min before mating did not prevent either LH release or ovulation. A single s.c. injection of (D-Phe2, L-Phe3, D-Phe6)-LHRH (6 mg/kg) given 30 min before mating in 4 rabbits resulted in a 30-60 min delay in the coitus-induced release of LH when compared with post-coital changes in the same animals injected with vehicle; however, all of the dose ovulated. When multiple dosages of 4 mg/kg (D-Phe2, L-Phe3, D-Phe6)-LHRH were administered 3-5 times as half-hourly intervals beginning 30 min prior to mating there was a considerable reduction in plasma LH elevations of at 0.5, 1.0, 2.0 and 4.0 h after mating and 3/5 treated rabbits showed partial or complete blockade of ovulation. Quite similar results were obtained with the same dosage of (D-Phe2, D-Trp3, D-Phe6)-LHRH. An early sharp peak in LH release and full ovulation were stimulated in 6 of 6 does by a single i.v. injection of synthetic LHRH (500 ng/kg). In another experiment, 3 half-hourly s.c. injections (4 mg/kg) of D-Phe2, L-Phe3, D-Phe6)-LHRH beginning 30 min before administering LHRH markedly reduced the rise in plasma LH (P < 0.01) and completely blocked ovulation in all of the same 6 animals. An unsuccessful attempt was made to provide a test animal for LHRH analogue investigations by implanting 4 cm of silastic tubing filled with crystalline estradiol (E2) s.c. in ovariectomized (OVX) and intact does. In OVX does the silastic E2 implants resulted in a progressive decline in the ability to release LH in response to mating at 6 and at 20 days after implantation. With ovaries present, the E2 implant permitted post-coital LH release and ovulation at 4 d [days] but not at 30 d post-implantation. At 30 d after removal of the E2 implant 3 out of 4 does had fully recovered the ability to release LH and ovulate post-coitally. Collectively, inhibitory analogues of LHRH can effectively block the ovulatory response to exogenous LHRH in rabbits, but coitally-induced LH release and ovulation are less susceptible to blockade by the analogues. Silastic E2 implants progressively and reversibly reduce the capacity of does to release LH after mating. [Contraceptive testing is discussed.].

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