Welt C K, Martin K A, Taylor A E, Lambert-Messerlian G M, Crowley W F, Smith J A, Schoenfeld D A, Hall J E
National Center for Infertility Research, Massachusetts General Hospital, Boston 02114, USA.
J Clin Endocrinol Metab. 1997 Aug;82(8):2645-52. doi: 10.1210/jcem.82.8.4138.
To isolate the impact of GnRH pulse frequency on FSH secretion and to examine the effect of differing levels of FSH on inhibin B secretion during the luteal-follicular transition, exogenous GnRH was administered to GnRH-deficient women using one of two regimens, and the results were compared to those in normal women. In the GnRH-deficient women, the GnRH pulse frequency was increased from every 4 h in the late luteal phase to every 90 min on the day of menses to mimic normal cycling women (physiological frequency transition; n = 8 studies) or the GnRH pulse frequency was kept constant at a late luteal phase frequency of every 4 h through the first 6 days of the subsequent early follicular phase of cycle 2 (slow frequency transition; n = 6 studies). The differential rise in FSH secretion induced in these studies allowed us to examine the subsequent contribution of varying levels of FSH to inhibin B secretion. A physiological regimen of GnRH during the luteal-follicular transition resulted in a rise in FSH and inhibin B levels that did not differ from that in normal cycling women and a normal follicular phase length. On the other hand, maintaining a luteal frequency of GnRH for 6 days into the subsequent early follicular phase produced FSH levels significantly lower than those in the physiological transition (P < 0.05), with the greatest difference seen on the day after menses (9.1 +/- 1.0 vs. 16.4 +/- 1.4 IU/L for the slow and physiological transition groups, respectively; P < 0.005), but no difference in LH. This slower rise of FSH secretion in the slow frequency group was associated with significantly lower inhibin B levels (43.3 +/- 21.5 vs. 140.0 +/- 24.4 pg/mL, mean days 1, 3, and 5; P < 0.02), a later doubling of estradiol from baseline (day 9.6 +/- 0.9 vs. day 5.6 +/- 0.1; P < 0.02), and a longer follicular phase length (16.0 +/- 1.4 vs. 11.6 +/- 0.9 days; P < 0.05) compared with those in the physiological transition group. In conclusion, during the luteal-follicular transition, the GnRH pulse frequency contributes to but is not solely responsible for the FSH rise that initiates folliculogenesis. Alteration of FSH dynamics induced by changes in GnRH pulse frequency in GnRH-deficient women provides evidence that FSH stimulates inhibin B production in the human. Timely follicular development indicated by both estradiol and inhibin B secretion appears to be dependent on the pattern of increase in FSH during the luteal-follicular transition.
为了分离促性腺激素释放激素（GnRH）脉冲频率对促卵泡生成素（FSH）分泌的影响，并研究在黄体-卵泡过渡期不同水平的FSH对抑制素B分泌的作用，采用两种方案之一对GnRH缺乏的女性给予外源性GnRH，并将结果与正常女性进行比较。在GnRH缺乏的女性中，GnRH脉冲频率从黄体晚期的每4小时一次增加到月经日的每90分钟一次，以模拟正常月经周期的女性（生理频率转变；n = 8项研究），或者在第2周期随后的卵泡早期的前6天，将GnRH脉冲频率维持在黄体晚期的每4小时一次的频率（缓慢频率转变；n = 6项研究）。这些研究中诱导的FSH分泌的差异升高使我们能够研究不同水平的FSH对抑制素B分泌的后续作用。黄体-卵泡过渡期GnRH的生理方案导致FSH和抑制素B水平升高，与正常月经周期女性相比无差异，且卵泡期长度正常。另一方面，在随后的卵泡早期将GnRH的黄体频率维持6天，产生的FSH水平显著低于生理转变组（P < 0.05），在月经后一天差异最大（缓慢转变组和生理转变组分别为9.1±1.0与16.4±1.4 IU/L；P < 0.005），但促黄体生成素（LH）无差异。缓慢频率组中FSH分泌的这种较慢升高与显著较低的抑制素B水平相关（第1、3和5天的平均值分别为43.3±21.5与140.0±24.4 pg/mL；P < 0.02），雌二醇从基线水平翻倍的时间较晚（分别为第9.6±0.9天与第5.6±0.1天；P < 0.02），与生理转变组相比卵泡期长度更长（分别为16.0±1.4与11.6±0.9天；P < 0.05）。总之，在黄体-卵泡过渡期，GnRH脉冲频率对启动卵泡生成的FSH升高有作用，但并非唯一原因。GnRH缺乏女性中GnRH脉冲频率变化引起的FSH动态改变提供了证据，表明FSH刺激人类抑制素B的产生。由雌二醇和抑制素B分泌表明的及时卵泡发育似乎依赖于黄体-卵泡过渡期FSH升高的模式。
