Kettel L M, Roseff S J, Chiu T C, Bangah M L, Vale W, Rivier J, Burger H G, Yen S S
Department of Reproductive Medicine, School of Medicine, University of California-San Diego, La Jolla 92093-0802.
J Clin Endocrinol Metab. 1991 Sep;73(3):644-9. doi: 10.1210/jcem-73-3-644.
The functional dependency of the dominant follicle on pulsatile gonadotropin inputs was evaluated by using a GnRH antagonist as a probe. Hormonal dynamics, particularly the relationship of FSH, estradiol, and inhibin, during and after the withdrawal of GnRH receptor blockade achieved by treatment with Nal-Glu GnRH antagonist (50 micrograms/kg, im) for 3 days in the midfollicular phase of the cycle (days 7-9) were ascertained. Daily blood samples were obtained for LH, FSH, estradiol (E2), progesterone, and immunoreactive inhibin (i-INH) measurements by RIA during 2 consecutive (control and treatment) cycles in 12 women. In 5 women, LH pulsatility was assessed by 10-min blood sampling for 12 h before, during, and after Nal-Glu treatment. The administration of Nal-Glu prolonged both follicular phase (14.0 +/- 0.5 vs. 19.7 +/- 0.8 days; P less than 0.0001) and total cycle length (28.1 +/- 0.5 vs. 34.1 +/- 1.2 days; P less than 0.0001). Gonadotropin suppression (50-60%) was achieved, as reflected by a marked decrease in mean LH levels (14.3 +/- 1.9 to 5.4 +/- 0.5; P less than 0.01) and LH pulse amplitude (5.5 +/- 0.7 to 2.4 +/- 0.3 IU/L; P less than 0.01) in response to Nal-Glu antagonist. The number of LH pulses was reduced (36%), but pulses remained discernible. Concentrations of FSH (10.8 +/- 1.4 to 5.9 +/- 0.4 IU/L; P less than 0.05), E2 (322.7 +/- 71.9 to 84.8 +/- 7.7 pmol/L; P less than 0.01) and i-INH (284.0 +/- 25.9 to 164.4 +/- 7.5 U/L; P less than 0.01) decreased concomitantly. Within 24-48 h of the last injection of Nal-Glu, all hormones had returned to pretreatment levels. This was followed by normal functional expression of follicular growth and maturation, as reflected by an increase in E2 and i-INH levels, timely ovulation, and normal luteal function. These findings indicate that an approximately 50% decline in gonadotropin support to the dominant follicle leads to functional arrest, but not demise, of the developing follicle(s) without triggering new folliculogenesis. The follicular apparatus retained its ability to reinitiate its original functionality once appropriate gonadotropin inputs were reinstated.
通过使用GnRH拮抗剂作为探针，评估优势卵泡对脉冲式促性腺激素输入的功能依赖性。确定了在月经周期卵泡中期（第7 - 9天）用Nal - Glu GnRH拮抗剂（50微克/千克，肌肉注射）治疗3天实现GnRH受体阻断期间及之后的激素动态变化，尤其是FSH、雌二醇和抑制素之间的关系。在12名女性的2个连续周期（对照和治疗周期）中，每天采集血样，通过放射免疫分析法测定LH、FSH、雌二醇（E2）、孕酮和免疫反应性抑制素（i - INH）。在5名女性中，在Nal - Glu治疗前、治疗期间和治疗后，通过每10分钟采集一次血样，持续12小时来评估LH脉冲性。Nal - Glu的给药延长了卵泡期（14.0±0.5天对19.7±0.8天；P＜0.0001）和整个周期长度（28.1±0.5天对34.1±1.2天；P＜0.0001）。促性腺激素受到抑制（50 - 60%），这表现为平均LH水平显著下降（14.3±1.9降至5.4±0.5；P＜0.01）以及LH脉冲幅度下降（5.5±0.7降至2.4±0.3 IU/L；P＜0.01），以响应Nal - Glu拮抗剂。LH脉冲数量减少（36%），但脉冲仍可辨别。FSH浓度（10.8±1.4降至5.9±0.4 IU/L；P＜0.05）、E2（322.7±71.9降至84.8±7.7 pmol/L；P＜0.01）和i - INH（284.0±25.9降至164.4±7.5 U/L；P＜0.01）随之下降。在最后一次注射Nal - Glu后的24 - 48小时内，所有激素都恢复到治疗前水平。随后卵泡生长和成熟出现正常功能表达，表现为E2和i - INH水平升高、适时排卵以及黄体功能正常。这些发现表明，对优势卵泡的促性腺激素支持下降约50%会导致发育中的卵泡功能停滞，但不会使其死亡，且不会引发新的卵泡生成。一旦恢复适当的促性腺激素输入，卵泡装置保留了重新启动其原始功能的能力。
