Batista M C, Cartledge T P, Zellmer A W, Nieman L K, Merriam G R, Loriaux D L
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Endocrinol Metab. 1992 Mar;74(3):565-70. doi: 10.1210/jcem.74.3.1740491.
Serum concentrations of progesterone begin to rise just before the midcycle gonadotropin surge that leads to ovulation. To examine the role of progesterone in the regulation of these events, we evaluated the effects of a low dose (1 mg/day, orally) of the antiprogesterone RU 486 on the timing of the gonadotropin surge and ovulation in normally cycling women. The drug or a placebo was given for 5 or 15 days, starting when the dominant follicle reached 14-16 mm. RU 486 consistently delayed the timing of the midcycle gonadotropin surge and the subsequent collapse of the dominant follicle, despite rising estradiol concentrations and normal follicular development. Unexpectedly, RU 486 also delayed the emergence of the periovulatory progesterone rise. The addition of progesterone (5-10 mg/day, im, for 2 days) to a 5-day course of RU 486 after the emergence of a mature follicle readily induced LH and FSH surges and completely reversed the effects of RU 486 at midcycle. Our results suggest that RU 486 delays the midcycle gonadotropin surge and ovulation by suppressing or antagonizing an ovarian progestational signal. Progesterone may, thus, represent the ultimate ovarian signal to the estrogen-primed hypothalamic-pituitary unit to trigger the gonadotropin surge that leads to ovulation.
在导致排卵的周期中期促性腺激素激增之前，血清孕酮浓度就开始升高。为了研究孕酮在调节这些事件中的作用，我们评估了低剂量（1毫克/天，口服）抗孕酮药物RU 486对正常月经周期女性促性腺激素激增时间和排卵时间的影响。当优势卵泡达到14 - 16毫米时开始，给予该药物或安慰剂5天或15天。尽管雌二醇浓度升高且卵泡发育正常，但RU 486持续延迟了周期中期促性腺激素激增的时间以及随后优势卵泡的破裂。出乎意料的是，RU 486还延迟了排卵期孕酮升高的出现。在成熟卵泡出现后，在5天疗程的RU 486基础上加用孕酮（5 - 10毫克/天，肌肉注射，共2天）可轻易诱导促黄体生成素（LH）和促卵泡生成素（FSH）激增，并在周期中期完全逆转RU 486的作用。我们的结果表明，RU 486通过抑制或拮抗卵巢孕激素信号来延迟周期中期促性腺激素激增和排卵。因此，孕酮可能是向雌激素预处理的下丘脑 - 垂体单位发出的最终卵巢信号，以触发导致排卵的促性腺激素激增。
