Hall J E, Bhatta N, Adams J M, Rivier J E, Vale W W, Crowley W F
Department of Medicine, Massachusetts General Hospital, Boston 02114.
J Clin Endocrinol Metab. 1991 May;72(5):993-1000. doi: 10.1210/jcem-72-5-993.
To examine the differential sensitivity of the ovary to temporary withdrawal of gonadotropin support at different stages of folliculogenesis and corpus luteum function, GnRH antagonist blockade of gonadotropin secretion was examined in 17 studies using the Nal-Glu GnRH antagonist. A vehicle control, antagonist treatment, and follow-up cycle format was used in each study. A previously determined ED100 dose of the Nal-Glu GnRH antagonist (150 micrograms/kg) or vehicle was administered sc every 24 h for 3 consecutive days in the midfollicular phase (MFP), late follicular phase (LFP), and midluteal phase (MLP). In studies in the MFP (n = 7), the largest follicle was 11 +/- 2 mm (mean +/- SEM), and the mean estradiol (E2) level was 220 +/- 44 pmol/L on the first day of antagonist administration. Administration of the antagonist resulted in a 75 +/- 6% suppression of LH (P less than 0.005), no significant change in FSH, and suppression of E2 to the assay detection limit (P less than 0.05). Total cycle length was increased compared to that of the vehicle control cycle (37.3 +/- 1.3 vs. 26.3 +/- 1.1 days; (P less than 0.005) due to prolongation of follicular phase length (P less than 0.005) and reinitiation of folliculogenesis. In the LFP (n = 5), the largest follicle was 16 +/- 1 mm (P less than 0.05 vs. MFP), and the E2 level was 394 +/- 95 pmol/L (P less than 0.05 vs. MFP) on the first day of antagonist administration. Antagonist administration resulted in a 65 +/- 6% suppression of LH (P less than 0.05), a 47 +/- 11% decrease in FSH (P less than 0.05), and no significant change in E2. Total cycle length was prolonged (32.4 +/- 2.2 vs. 25.6 +/- 0.4 days; P less than 0.05) due to an increase in follicular phase length (P less than 0.02); however, the prolongation of the follicular phase was significantly less than that of the MFP (8.0 +/- 1.5 vs. 15.1 +/- 0.1 days; P less than 0.001), suggesting ovulation from the initial dominant follicle. In studies in the MLP (n = 5), LH, E2, and progesterone decreased to the assay detection limit after antagonist administration, while FSH decreased by 36 +/- 4% (P less than 0.05). Menstrual bleeding occurred within 24-48 h of the final Nal-Glu antagonist injection.(ABSTRACT TRUNCATED AT 400 WORDS)
为研究卵巢在卵泡发生和黄体功能不同阶段对促性腺激素支持暂时撤除的差异敏感性，在17项研究中使用Nal-Glu GnRH拮抗剂检测促性腺激素分泌的GnRH拮抗剂阻断作用。每项研究均采用载体对照、拮抗剂治疗和后续周期模式。在卵泡中期（MFP）、卵泡晚期（LFP）和黄体中期（MLP），每24小时皮下注射一次预先确定的Nal-Glu GnRH拮抗剂ED100剂量（150微克/千克）或载体，连续3天。在MFP的研究（n = 7）中，拮抗剂给药第一天最大卵泡为11±2毫米（均值±标准误），平均雌二醇（E2）水平为220±44皮摩尔/升。给予拮抗剂导致LH抑制75±6%（P<0.005），FSH无显著变化，E2抑制至检测下限（P<0.05）。与载体对照周期相比，总周期长度增加（37.3±1.3天对26.3±1.1天；P<0.005），原因是卵泡期长度延长（P<0.005）和卵泡发生重新启动。在LFP的研究（n = 5）中，拮抗剂给药第一天最大卵泡为16±1毫米（与MFP相比，P<0.05），E2水平为394±95皮摩尔/升（与MFP相比，P<0.05）。给予拮抗剂导致LH抑制65±6%（P<0.05），FSH降低47±11%（P<0.05），E2无显著变化。总周期长度延长（32.4±2.2天对25.6±0.4天；P<0.05），原因是卵泡期长度增加（P<0.02）；然而，卵泡期延长明显小于MFP（8.0±1.5天对15.1±0.1天；P<0.001），提示从初始优势卵泡排卵。在MLP的研究（n = 5）中，给予拮抗剂后LH、E2和孕酮降至检测下限，而FSH降低36±4%（P<0.05）。末次Nal-Glu拮抗剂注射后24 - 48小时内发生月经出血。（摘要截断于400字）
