Phelps C P, Coy D H, Schally A V, Sawyer C H
Endocrinology. 1977 Jun;100(6):1526-32. doi: 10.1210/endo-100-6-1526.
Plasma LH 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 sc) to does 30 min before mating did not prevent either LH release or ovulation. However, a single sc injection of (D-Phe2, L-Phe3, D-Phe6y-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 does ovulated. When multiple dosages of 4 mg/kg (D-Phe2, L-Phe3, D-Phe6)-LHRH were administered 3-5 times at half-hourly intervals beginning 30 min prior to mating there was a considerable reduction in plasma LH elevations 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 out of 6 does by a single iv injection of synthetic LHRH (500 ng/kg). However, in another experiment, three half-hourly sc 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 less than 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) sc 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 but not at 30 d post-implantation. At 30 d after removal of the E2 implant three out of four does had fully recovered the ability to release LH and ovulate post-coitally. Collectively, these results indicate that inhibitory analogues of LHRH can effectively block the ovulatory response to exogenous LHRH in rabbits, but that coitally-induced LH release and ovulation are less susceptible to blockade by the analogues. Silastic E2 implants, however, progressively and reversibly reduce the capacity of does to release LH after mating.
在雌性兔子与经验丰富的雄性兔子交配前后，研究了几种促黄体生成激素释放激素（LHRH）抑制类似物给药后血浆促黄体生成素（LH）水平和排卵情况。在交配前30分钟给母兔皮下注射（D-苯丙氨酸2，D-亮氨酸6）-LHRH（1.5毫克/千克），既未阻止LH释放，也未阻止排卵。然而，在4只兔子交配前30分钟皮下注射一次（D-苯丙氨酸2，L-苯丙氨酸3，D-苯丙氨酸6）-LHRH（6毫克/千克），与注射赋形剂的同组动物交配后变化相比，交配诱导的LH释放延迟了30 - 60分钟；然而，所有母兔均排卵。当从交配前30分钟开始，每隔半小时给予4毫克/千克（D-苯丙氨酸2，L-苯丙氨酸3，D-苯丙氨酸6）-LHRH多次剂量（3 - 5次）时，交配后0.5、1.0、2.0和4.0小时血浆LH升高明显降低，3/5接受治疗的兔子排卵部分或完全受阻。用相同剂量的（D-苯丙氨酸2，D-色氨酸3，D-苯丙氨酸6）-LHRH也得到了非常相似的结果。6只母兔单次静脉注射合成LHRH（500纳克/千克）后，均出现LH释放的早期急剧峰值和完全排卵。然而，在另一项实验中，在给予LHRH前30分钟开始，每隔半小时皮下注射三次（4毫克/千克）（D-苯丙氨酸2，L-苯丙氨酸3，D-苯丙氨酸6）-LHRH，显著降低了血浆LH的升高（P＜0.01），并完全阻止了同组6只动物的排卵。通过在去卵巢（OVX）和完整母兔皮下植入4厘米填充结晶雌二醇（E2）的硅橡胶管，试图为LHRH类似物研究提供实验动物，但未成功。在去卵巢母兔中，硅橡胶E2植入物导致植入后6天和20天对交配释放LH的能力逐渐下降。卵巢存在时，E2植入物允许交配后LH释放和在植入后4天排卵，但在植入后30天不排卵。在去除E2植入物30天后，4只母兔中有3只已完全恢复交配后释放LH和排卵的能力。总体而言，这些结果表明，LHRH抑制类似物可有效阻断兔子对外源性LHRH的排卵反应，但交配诱导的LH释放和排卵对类似物的阻断较不敏感。然而，硅橡胶E2植入物可逐渐且可逆地降低母兔交配后释放LH的能力。
