Sánchez-Criado J E, Tébar M, Ruiz A, Padrón L
Department of Physiology, Faculty of Medicine, University of Cordoba, Spain.
Eur J Endocrinol. 1997 Sep;137(3):281-6. doi: 10.1530/eje.0.1370281.
Administration of the steroid antagonist RU486 to cyclic rats at pro-oestrus blunts the preovulatory surge of LH and suppresses the first and second surges of FSH. In addition, administration of oestradiol to RU486-treated rats reactivates the LH surge the following day. The present study explored the effects of RU486 (4 mg/0.2 ml oil), administered at 0800 h on the day of pro-oestrus, on serum FSH and LH concentrations through oestrus and early metoestrus. RU486 induced a hypersecretion of FSH, which started at 1400 h on the day of oestrus and was maintained until 0800 h on the day of metoestrus. Because the timing and magnitude of this secretion of FSH were similar to those of the periovulatory secretion of FSH during pro-oestrus and early oestrus in intact cyclic rats, we investigated the effects of: 1) LHRH antagonist (LHRHa) injected at either 0900 h or 2000 h on the day of oestrus, 2) oestradiol benzoate injected at 1600 h on the day of pro-oestrus and at 0900 h on the day of oestrus, 3) bovine follicular fluid (bFF) given either at 1100 h or at 2000 h on the day of oestrus, or 4) adrenalectomy (ADX) at 1100 h on the day of oestrus, on serum FSH and LH concentrations at 1800 h on the day of oestrus and at 0200 h on the day of metoestrus in rats injected with RU486 at pro-oestrus. The results showed that 1) both components (late oestrus and early metoestrus) of FSH hypersecretion in RU486-injected rats in pro-oestrus were inhibited by oestradiol benzoate and bFF, 2) the metoestrous component was not affected by LHRHa, whereas the oestrous component was partially reduced, and 3) ADX partially reduced serum FSH concentrations only on the day of metoestrus, possibly because, as the serum concentrations of corticosterone reflected, the antiglucocorticoid activity of 4 mg RU486 lasted only 24 h. The results support the hypothesis that blockade of progesterone actions at pro-oestrus results in the maintenance of the daily neural signal that activates the release of gonadotrophins. Whereas the expression of LH secretion requires high levels of oestradiol, FSH secretion is expressed against a background of low oestradiol levels. The results of this study also indicate that the release of FSH during oestrus and metoestrus in rats injected with RU486 at pro-oestrus is a consequence of the lack of ovarian negative feedback inhibition on the pituitary.
在发情前期给处于发情周期的大鼠注射类固醇拮抗剂RU486，会减弱促黄体生成素（LH）的排卵前激增，并抑制促卵泡激素（FSH）的第一次和第二次激增。此外，给经RU486处理的大鼠注射雌二醇会在第二天重新激活LH激增。本研究探讨了在发情前期08:00给予RU486（4毫克/0.2毫升油剂）对整个发情期和发情后期血清FSH和LH浓度的影响。RU486诱导了FSH的分泌过多，这在发情当天14:00开始，并持续到发情后期的08:00。由于这种FSH分泌的时间和幅度与完整发情周期大鼠在发情前期和发情早期促排卵时FSH的分泌相似，我们研究了以下因素的影响：1）在发情当天09:00或20:00注射促性腺激素释放激素拮抗剂（LHRHa）；2）在发情前期16:00和发情当天09:00注射苯甲酸雌二醇；3）在发情当天11:00或20:00给予牛卵泡液（bFF）；4）在发情当天11:00进行肾上腺切除术（ADX），这些因素对在发情前期注射RU486的大鼠在发情当天18:00和发情后期02:00时血清FSH和LH浓度的影响。结果表明：1）发情前期注射RU486的大鼠FSH分泌过多的两个阶段（发情后期和发情早期）均受到苯甲酸雌二醇和bFF的抑制；2）发情后期阶段不受LHRHa影响，而发情期阶段部分降低；3）ADX仅在发情后期部分降低血清FSH浓度，这可能是因为，正如皮质酮的血清浓度所反映的那样，4毫克RU486的抗糖皮质激素活性仅持续24小时。这些结果支持了以下假设：发情前期孕酮作用的阻断导致激活促性腺激素释放的每日神经信号得以维持。虽然LH分泌的表达需要高水平的雌二醇，但FSH分泌是在低水平雌二醇的背景下表达的。本研究结果还表明，发情前期注射RU486的大鼠在发情期和发情后期FSH的释放是由于卵巢对垂体缺乏负反馈抑制的结果。
