Sánchez-Criado J E, Bellido C, Galiot F, López F J, Gaytán F
Department of Physiology, Faculty of Medicine, University of Córdoba, Spain.
Biol Reprod. 1990 May-Jun;42(5-6):877-86. doi: 10.1095/biolreprod42.6.877.
The purpose of these experiments was to investigate the mechanism of the anovulatory action of antiprogesterone RU486 (RU486) in rats by studying its effects on follicular growth, secretion of gonadotropins and ovarian steroids, and ovulation. Rats with 4-day estrous cycles received injections (s.c.) of either 0.2 ml oil or 0.1, 1, or 5 mg of RU486 at 0800 and 1600 h on metestrus, diestrus, and proestrus. At the same times, they were bled by jugular venipuncture to determine serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 beta-estradiol (E), and progesterone (P). On the morning of the day after proestrus, ovulation and histological features of the ovary were recorded. Rats from each group were killed on each day of ovarian cycle to assess follicular development. Rats treated similarly were decapitated at the time of the ovulatory LH surge and blood was collected to measure LH. The serum levels of LH increased and those of FSH decreased during diestrus in rats treated with RU486. Neither E nor P levels differed among the groups. Treatment with RU486 caused both a blockade of the ovulation and an increase in ovarian weight in a dose-dependent manner. At the time of the autopsy (the expected day of ovulation), rats treated with 1 mg RU486 had ovaries presenting both normal and post-ovulatory follicles and unruptured luteinized follicles. Rats treated with 5 mg RU486 presented post-ovulatory follicles without signs of luteinization. The number of follicles undergoing atresia increased in rats treated with RU486. Rats treated with 5 mg RU486 exhibited a significant decrease in ovulatory LH release. The mechanism by which RU486 produces the ovulatory impairment in rats seems to be dual: first, by inducing inadequate follicular development at the time of the LH surge and second, by reducing the amount of ovulatory LH released. The physiological events-decreased basal FSH secretion and follicular atresia-that result from use of RU486 cannot be elucidated from these experiments and should be investigated further.
这些实验的目的是通过研究抗孕激素RU486（米非司酮）对卵泡生长、促性腺激素和卵巢甾体激素分泌以及排卵的影响，来探讨其在大鼠中无排卵作用的机制。处于4天发情周期的大鼠在间情期、动情后期和动情前期的08:00和16:00接受皮下注射，分别注射0.2 ml油剂或0.1、1或5 mg的RU486。同时，通过颈静脉穿刺取血，以测定血清中促黄体生成素（LH）、促卵泡生成素（FSH）、17β-雌二醇（E）和孕酮（P）的浓度。在动情前期后的早晨，记录排卵情况和卵巢的组织学特征。在卵巢周期的每一天，处死每组中的大鼠以评估卵泡发育情况。对处理方式相同的大鼠，在排卵性LH峰出现时断头取血，以测定LH。用RU486处理的大鼠在动情后期血清LH水平升高，FSH水平降低。各组间E和P水平均无差异。用RU486处理导致排卵受阻和卵巢重量增加，且呈剂量依赖性。在尸检时（预期的排卵日），用1 mg RU486处理的大鼠卵巢中既有正常卵泡和排卵后卵泡，也有未破裂的黄素化卵泡。用5 mg RU486处理的大鼠有排卵后卵泡，但无黄素化迹象。用RU486处理的大鼠中闭锁卵泡的数量增加。用5 mg RU486处理的大鼠排卵性LH释放显著减少。RU486在大鼠中导致排卵障碍的机制似乎是双重的：首先，在LH峰出现时诱导卵泡发育不足；其次，减少排卵性LH的释放量。使用RU486所导致的生理事件——基础FSH分泌减少和卵泡闭锁——无法从这些实验中得到阐明，应进一步研究。
