Rossmanith W G, Mortola J F, Yen S S
Department of Reproductive Medicine, School of Medicine, University of California-San Diego, La Jolla 92093.
J Clin Endocrinol Metab. 1988 Oct;67(4):695-700. doi: 10.1210/jcem-67-4-695.
While compelling evidence indicates a pivotal role for endogenous opioids in the regulation of GnRH-LH pulsatile activity during the late follicular and luteal phases of the menstrual cycle, the participation, if any, of the opioidergic mechanism in the initiation of the midcycle surge has not been examined. Accordingly, we measured serum LH, FSH, estradiol (E2) and progesterone (P4) levels daily during 2 consecutive cycles in 12 normal cycling women. After a control cycle, each woman was infused with naloxone (30 micrograms/kg.h) for 24 h starting 3 days before the anticipated spontaneous midcycle surge. Blood samples were obtained at 15-min intervals for 8 h before, during, and 16 h after the naloxone infusion. Serum LH and FSH concentrations were measured in all samples, and serum E2 and P4 concentrations at 2-h intervals. Pulsatile LH secretion was analyzed using the cluster program. The opioidergic blockade elicited a robust increase in LH pulsatile activity and a 3-fold rise in serum FSH levels in 6 of the 12 women. This increased gonadotropin secretion lasted more than 24 h and was characterized by a progressive increase in LH pulse amplitude, which was 9-fold greater during the last 8 h of naloxone infusion [mean LH pulse amplitude, 36.5 +/- 4.5 (+/- SE) vs. 4.1 +/- 0.4 IU/L; P less than 0.001]. This increase was accompanied by a corresponding increase in transverse mean serum LH levels (83.3 +/- 13 vs. 20.7 +/- 3.2 IU/L; P less than 0.001), but no alteration of the interpulse interval (93 +/- 11 vs. 85 +/- 4 min). The peak serum LH concentrations exceeded 100 IU/L in all 6 of these women. This naloxone-advanced gonadotropin surge, resembling closely the spontaneous midcycle surge, resulted in a significantly shortened (P less than 0.001) follicular phase and a more than 2-fold elevation of serum P4, followed by assumed ovulation and normal luteal function. These 6 women had serum E2 levels immediately before naloxone infusion that were comparable to those during the preovulatory peak during the control cycle. In the 6 women who did not have a naloxone-induced increase in gonadotropin secretion the preinfusion serum E2 levels were substantially lower (P less than 0.001) than the values during the control cycle. These findings suggest that a transient decrease in opioidergic activity may contribute to the initiation of the midcycle gonadotropin surge in women.
虽然有力证据表明内源性阿片肽在月经周期卵泡晚期和黄体期GnRH-LH脉冲式活动的调节中起关键作用，但阿片肽能机制在月经周期中期高峰启动过程中（若有）的参与情况尚未得到研究。因此，我们对12名正常月经周期女性连续两个周期每天测量血清LH、FSH、雌二醇（E2）和孕酮（P4）水平。在一个对照周期后，每名女性在预期的自发月经周期中期高峰前3天开始接受24小时的纳洛酮（30微克/千克·小时）输注。在纳洛酮输注前8小时、输注期间和输注后16小时，每隔15分钟采集血样。对所有样本测量血清LH和FSH浓度，每隔2小时测量血清E2和P4浓度。使用聚类程序分析LH的脉冲式分泌。阿片肽能阻断使12名女性中的6名LH脉冲式活动显著增加，血清FSH水平升高3倍。这种促性腺激素分泌增加持续超过24小时，其特征是LH脉冲幅度逐渐增加，在纳洛酮输注的最后8小时内增加了9倍[平均LH脉冲幅度，36.5±4.5（±SE）对4.1±0.4 IU/L；P<0.001]。这种增加伴随着横向平均血清LH水平相应增加（83.3±13对20.7±3.2 IU/L；P<0.001），但脉冲间期无改变（93±11对85±4分钟）。这6名女性的血清LH峰值浓度均超过100 IU/L。这种纳洛酮提前引发的促性腺激素高峰与自发月经周期中期高峰非常相似，导致卵泡期显著缩短（P<0.001），血清P4升高超过2倍，随后假定发生排卵且黄体功能正常。这6名女性在纳洛酮输注前的血清E2水平与对照周期排卵前高峰时相当。在另外6名未出现纳洛酮诱导的促性腺激素分泌增加的女性中，输注前血清E2水平显著低于对照周期的值（P<0.001）。这些发现表明，阿片肽能活性的短暂降低可能有助于女性月经周期中期促性腺激素高峰的启动。
