de Koning J
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratory, University of Leiden, The Netherlands.
Hum Reprod. 1995 Nov;10(11):2854-61. doi: 10.1093/oxfordjournals.humrep.a135807.
The stabilization of low luteinizing hormone (LH) concentrations during the period of the ovarian cycle preceding the mid-cycle LH surge seems to be of importance for embryo viability and survival. Several studies have stressed the importance of the timely excess of threshold levels of LH for optimal oocyte quality: LH already initiates the resumption of meiosis when a relatively low threshold level is reached, whereas a further outburst of LH release is necessary to reach the threshold level to induce ovulation. Hence, the mechanism of LH release should have the ability, on the one hand, to limit the LH secretion rate, and on the other, to allow an increased secretion rate, as during the LH surge. The functional antagonistic coupling of gonadotrophin-releasing hormone (GnRH) and the ovarian protein gonadotrophin surge-inhibiting factor or -attenuating factor (GnSIF/AF) provides such a mode of action for the control of LH concentration during the ovarian cycle. One of the important regulatory steps in this process is the de-novo synthesis of the so far unidentified pituitary proteins induced by GnRH. The induction of these proteins is a prerequisite for the increase in the rate of LH release. Because their synthesis is a time-consuming process, the effect becomes visible in the typical biphasic pituitary LH responses to the pulsatile or continuous administration of GnRH: initially low, with an increase after some time. This phenomenon is also known as the GnRH self-priming action. It is assumed that the synthesis of these self-priming-associated proteins is necessary to eliminate the inhibitory effect of GnSIF/AF. GnSIF/AF eliminates the effect of self-priming by neutralizing the biological activity of the pituitary proteins, which are responsible for the increased rate of LH release. Thus, the pituitary gland is kept in a GnRH-hyporesponsive state. The major advantage of such a slow protein synthesis-dependent regulatory mechanism is that it prevents sudden increases in the LH secretion rate in response to GnRH. Thus it stabilizes low LH concentrations to prevent the premature reinitiation of meiosis. However, the enhanced secretion of GnRH and/or the suppressed release or action of GnSIF/AF may finally lead to the restoration of the intrinsic LH responsiveness of the gonadotrophs at the start of the mid-cycle LH surge. The antagonistic interaction between GnRH and GnSIF/AF, and its implication in the control of LH release under physiological and pathological conditions, are discussed.
在月经周期中期促黄体生成素（LH）高峰之前的卵巢周期期间，低促黄体生成素浓度的稳定似乎对胚胎的活力和存活至关重要。多项研究强调了促黄体生成素阈值水平及时超过对最佳卵母细胞质量的重要性：当达到相对较低的阈值水平时，促黄体生成素就已启动减数分裂的恢复，而促黄体生成素释放的进一步爆发对于达到诱导排卵的阈值水平是必要的。因此，促黄体生成素释放机制一方面应具有限制促黄体生成素分泌速率的能力，另一方面应能允许分泌速率增加，如在促黄体生成素高峰期间。促性腺激素释放激素（GnRH）与卵巢蛋白促性腺激素高峰抑制因子或衰减因子（GnSIF/AF）的功能性拮抗偶联为控制卵巢周期中的促黄体生成素浓度提供了这样一种作用方式。这一过程中一个重要的调节步骤是GnRH诱导的迄今未鉴定的垂体蛋白的从头合成。这些蛋白的诱导是促黄体生成素释放速率增加的先决条件。由于它们的合成是一个耗时的过程，这种效应在垂体对GnRH脉冲式或持续给药的典型双相促黄体生成素反应中可见：最初较低，一段时间后增加。这种现象也被称为GnRH自启动作用。据推测，这些与自启动相关的蛋白的合成对于消除GnSIF/AF的抑制作用是必要的。GnSIF/AF通过中和负责促黄体生成素释放速率增加的垂体蛋白的生物活性来消除自启动的作用。因此，垂体处于GnRH低反应状态。这种依赖于缓慢蛋白质合成的调节机制的主要优点是它可防止促黄体生成素分泌速率因GnRH而突然增加。因此它稳定低促黄体生成素浓度以防止减数分裂过早重新启动。然而，GnRH分泌增强和/或GnSIF/AF释放或作用受抑制最终可能导致在月经周期中期促黄体生成素高峰开始时促性腺细胞内在促黄体生成素反应性的恢复。文中讨论了GnRH与GnSIF/AF之间的拮抗相互作用及其在生理和病理条件下对促黄体生成素释放控制的意义。
