Lado Abeal J, Rey Losada C, Cabezas Agricola J M, Cabezas-Cerrato J
Cátedra de Patologia General (Departamento de Medicina), Hospital General de Galicia, Spain.
Clin Endocrinol (Oxf). 1994 Jan;40(1):127-31. doi: 10.1111/j.1365-2265.1994.tb02454.x.
It is not known whether gamma-aminobutyric acid (GABA) is involved in control of pulsatile LH secretion in human beings. Previous work by our group has shown that manipulation of the GABAergic system with sodium valproate does not affect pulsatile LH secretion in normal women in the late follicular phase. However, it has been suggested that steroid levels are critical for the influence of GABA upon hormone secretion; in particular, progesterone has been said to enhance inhibition by GABA. In this work we studied the effect of sodium valproate on pulsatile LH secretion in medium-late luteal phase of normal women.
Six normal young women were studied over an 8-hour period in two successive menstrual cycles. On each occasion blood samples were taken every 10 minutes between 1000 and 1800 h. We administered 400 mg of sodium valproate every 8 hours on the 7 days preceding their second cycle and additional 400 mg at 0900 and 1400 h on the day of the study. Ovulation day was estimated by means of serial ovarian ultrasound examinations and confirmed by serum progesterone concentrations.
In each cycle, LH, oestradiol and progesterone were determined by radioimmunoassay and sodium valproate by repolarization fluorescence spectrophotometry. The series of LH levels was smoothed for 1-minute sampling periods by means of a spline function and analysed by means of a program developed in our laboratory and written in Fortran 77. The program deconvolved the signal and calculated the pulse area, pulse duration, interpulse interval and number of pulses. LH pulse identification on the deconvolved signals was performed using our own method based on Friedman's non-parametric statistic. The statistical significance of differences between parameters was estimated using the Mann-Whitney test and Wilcoxon signed rank test.
There were no significant differences in LH pulse area, pulse duration, interpulse interval or number of pulses with the administration of sodium valproate.
Activation of the GABAergic system with sodium valproate had no biologically significant effect on the mid-late luteal phase pulsatile LH secretion in normal women.
尚不清楚γ-氨基丁酸（GABA）是否参与人类促黄体生成素（LH）脉冲式分泌的调控。我们团队之前的研究表明，用丙戊酸钠对GABA能系统进行调控，并不会影响正常女性卵泡晚期的LH脉冲式分泌。然而，有研究表明，类固醇水平对于GABA对激素分泌的影响至关重要；特别是，据说孕酮可增强GABA的抑制作用。在本研究中，我们探讨了丙戊酸钠对正常女性黄体中晚期LH脉冲式分泌的影响。
在两个连续的月经周期中，对6名正常年轻女性进行了为期8小时的研究。每次研究时，于10:00至18:00期间每隔10分钟采集一次血样。在第二个周期前7天，每8小时给予400mg丙戊酸钠，并在研究当天的09:00和14:00额外给予400mg。通过系列卵巢超声检查估算排卵日，并通过血清孕酮浓度进行确认。
在每个周期中，采用放射免疫分析法测定LH、雌二醇和孕酮水平，采用复极化荧光分光光度法测定丙戊酸钠水平。通过样条函数对1分钟采样期的LH水平系列进行平滑处理，并使用我们实验室用Fortran 77编写的程序进行分析。该程序对信号进行反卷积处理，并计算脉冲面积、脉冲持续时间、脉冲间期和脉冲数量。使用基于弗里德曼非参数统计量的我们自己的方法，对反卷积信号上的LH脉冲进行识别。使用曼-惠特尼检验和威尔科克森符号秩检验评估参数之间差异的统计学意义。
给予丙戊酸钠后，LH脉冲面积、脉冲持续时间、脉冲间期或脉冲数量均无显著差异。
用丙戊酸钠激活GABA能系统，对正常女性黄体中晚期的LH脉冲式分泌没有生物学上的显著影响。
