Brännström M
Department of Obstetrics and Gynaecology, University of Adelaide, Queen Elizabeth Hospital, South Australia.
Contraception. 1993 Oct;48(4):393-402. doi: 10.1016/0010-7824(93)90084-k.
The antigestagen mifepristone (RU 486) acts by blocking the progesterone receptor. Mifepristone has been used clinically for medical termination of pregnancy. It has recently also been shown that it can be used as an effective contraceptive agent in many species including the human. This contraceptive effect is acquired through prolonged exposure to mifepristone during the follicular phase and has been linked to disrupted folliculogenesis and inhibition of the LH surge. In the present study it is tested if mifepristone inhibits ovulation by a direct action on the ovary at the time of the LH surge. Preovulatory rat ovaries from immature Sprague-Dawley rats primed with 20IU of equine CG were perfused in vitro for 20 h in the presence of LH and 3-isobutyl-1-methylxanthine (IBMX) to induce ovulations. Mifepristone was added to study the effect on ovulation rate and ovarian steroidogenesis. Unstimulated control ovaries did not ovulate whereas addition of ovine LH (0.1 microgram/ml) and IBMX (0.2mM) resulted in 17.6 +/- 2.7 ovulations per treated ovary. Presence of mifepristone at 1 microM did not significantly inhibit LH+IBMX-induced ovulation (13.0 +/- 1.2) whereas mifepristone at 50 microM significantly (p < 0.01) inhibited ovulation (2.8 +/- 1.4). When the latter dosage of mifepristone (50 microM) was added 4h after LH+IBMX, no inhibitory effect was seen (17.2 +/- 3.0). Progesterone and estradiol release was significantly increased by LH+IBMX over the control group. Presence of mifepristone at any tested dose or time of addition did not significantly change the LH+IBMX-stimulated steroid release. It is concluded that mifepristone inhibits ovulation in the rat at the ovarian level when present just before LH stimulation but not when administered 4h into the ovulatory process.
抗孕激素米非司酮（RU 486）通过阻断孕酮受体发挥作用。米非司酮已在临床上用于药物终止妊娠。最近还表明，它在包括人类在内的许多物种中都可作为一种有效的避孕剂。这种避孕效果是通过在卵泡期长时间接触米非司酮获得的，并且与卵泡生成紊乱和促黄体生成素高峰的抑制有关。在本研究中，测试了米非司酮在促黄体生成素高峰时是否通过对卵巢的直接作用来抑制排卵。将用20国际单位马绒毛膜促性腺激素预处理的未成熟斯普拉格-道利大鼠的排卵前卵巢在体外于促黄体生成素和3-异丁基-1-甲基黄嘌呤（IBMX）存在的情况下灌注20小时以诱导排卵。添加米非司酮以研究其对排卵率和卵巢类固醇生成的影响。未受刺激的对照卵巢不排卵，而添加羊促黄体生成素（0.1微克/毫升）和IBMX（0.2毫摩尔）导致每个处理的卵巢有17.6±2.7个卵子排出。1微摩尔的米非司酮并未显著抑制促黄体生成素+IBMX诱导的排卵（13.0±1.2），而50微摩尔的米非司酮则显著（p<0.01）抑制排卵（2.8±1.4）。当在促黄体生成素+IBMX后4小时添加后一种剂量的米非司酮（50微摩尔）时，未观察到抑制作用（17.2±3.0）。与对照组相比，促黄体生成素+IBMX使孕酮和雌二醇的释放显著增加。在任何测试剂量或添加时间存在米非司酮均未显著改变促黄体生成素+IBMX刺激的类固醇释放。得出的结论是，米非司酮在促黄体生成素刺激前存在时在卵巢水平抑制大鼠排卵，但在排卵过程开始4小时后给药则无此作用。
