Mais V, Kazer R R, Cetel N S, Rivier J, Vale W, Yen S S
J Clin Endocrinol Metab. 1986 Jun;62(6):1250-5. doi: 10.1210/jcem-62-6-1250.
A potent GnRH antagonist, [Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6]GnRH (4F-Antag), was used as a probe to determine the relative dependency of ovarian cyclicity on pulsatile gonadotropin secretion. 4F-Antag was administered in a dose of 80 micrograms/kg sc twice a day for 3 consecutive days during different phases of the menstrual cycle. This treatment resulted in a prompt attenuation of pulsatile gonadotropin secretion in all women studied. Maximal suppression of gonadotropin levels, expressed as percent change from baseline, averaged 48% for LH and 22% for FSH. The reduced pulsatile gonadotropin release induced by 4F-Antag administration during the early follicular phase resulted in a significant decrease in serum estradiol levels during the period of treatment and was followed by a prolongation of follicular phase (2.4 days) and cycle length (3.5 days), but no alteration of subsequent cyclic ovarian steroid profiles compared to control cycles. Treatment initiated during the midfollicular phase 4-6 days before the expected LH surge resulted in a more dramatic decline in serum estradiol levels and prolongation of follicular phase length by 5-6 days compared to control cycles. Normal luteal function was preserved. These alterations were compatible with induction of the demise of the dominant follicle followed by the reinitiation of follicular recruitment. Administration of 4F-Antag during the midluteal phase resulted in rapid falls in serum estradiol and progesterone levels and the onset of menstrual bleeding in all women. The luteolytic effect of 4F-Antag was completely negated by the administration of hCG. These data indicate that 4F-Antag interferes with ongoing cyclic ovarian function by reducing pulsatile gonadotropin stimulation, which disrupts folliculogenic processes and induces the demise of the corpus luteum. From these findings we infer that the functional integrity of ovarian cyclicity is remarkably sensitive to brief (3 days) and partial reduction in pulsatile gonadotropin secretion.
一种强效促性腺激素释放激素（GnRH）拮抗剂[Ac-δ3-Pro1，对氟-D-苯丙氨酸2，D-色氨酸3,6]GnRH（4F-Antag）被用作探针，以确定卵巢周期性对脉冲式促性腺激素分泌的相对依赖性。在月经周期的不同阶段，每天两次皮下注射剂量为80微克/千克的4F-Antag，连续注射3天。该治疗导致所有受试女性的脉冲式促性腺激素分泌迅速减弱。以相对于基线的百分比变化表示的促性腺激素水平的最大抑制，促黄体生成素（LH）平均为48%，促卵泡生成素（FSH）为22%。在卵泡早期给予4F-Antag导致脉冲式促性腺激素释放减少，在治疗期间血清雌二醇水平显著下降，随后卵泡期延长（2.4天）和周期长度延长（3.5天），但与对照周期相比，随后的卵巢类固醇周期性变化没有改变。在预期的LH峰前4 - 6天的卵泡中期开始治疗，与对照周期相比，血清雌二醇水平下降更显著，卵泡期长度延长5 - 6天。黄体功能保持正常。这些改变与优势卵泡的消亡诱导以及随后卵泡募集的重新启动相一致。在黄体中期给予4F-Antag导致所有女性血清雌二醇和孕酮水平迅速下降并出现月经出血。4F-Antag的黄体溶解作用被人绒毛膜促性腺激素（hCG）给药完全抵消。这些数据表明，4F-Antag通过减少脉冲式促性腺激素刺激来干扰正在进行的卵巢周期性功能，这会破坏卵泡生成过程并诱导黄体的消亡。从这些发现中我们推断，卵巢周期性的功能完整性对脉冲式促性腺激素分泌的短暂（3天）和部分减少非常敏感。
