Lado-Abeal J, Liz J L, Rey C, Febrero M, Cabezas-Cerrato J
Endocrinology and Nutrition Service, General Hospital of Galicia, Santiago de Compostela School of Medicine, Spain.
Eur J Endocrinol. 1996 Sep;135(3):293-8. doi: 10.1530/eje.0.1350293.
It is well established that valproate increases hypothalamic concentrations of gamma-aminobutyric acid (GABA). Although little research has been done on the role of GABA in the control of pulsatile luteinizing hormone (LH) secretion in humans, our group recently found that administration of valproate had no significant effect on pulsatile LH secretion in late follicular and mid-late luteal phase normal women. However, the results of several studies of rats suggest that GABAergic regulation of LH secretion may depend on steroid levels. The objective of this work was to determine whether regular administration of sodium valproate inhibits pulsatile LH secretion in ovariectomized women. Twelve women who had undergone ovariectomy for causes other than malignant tumors were each studied in two 8 h sessions, in each of which blood samples were taken every 5 min. The first session was the control; for the second. 400 mg of sodium valproate was administered every 8 h during the seven preceding days and at 08.00 h and 14.00 h on the day of the study session. Serum valproate was determined by repolarization fluorescence spectrophotometry, and LH, estradiol and progesterone by radioimmunoassay. The serum LH series were subjected to a deconvolution procedure to reconstruct the pattern of pituitary LH secretion. Luteinizing hormone pulses were identified by the authors' non-parametric method. Control and post-valproate results were compared with regard to number of pulses, pulse duration, the quantity of LH secreted in each pulse, interpulse interval and mean serum LH level. There was no statistically significant difference between control and post-valproate results for any of the variables considered. It is concluded that sustained serum valproate levels do not alter pulsatile secretion of LH in ovariectomized women. This implies that, in humans, GABA is probably not a decisive factor in the regulation of the GnRH pulse generator.
丙戊酸盐可提高下丘脑γ-氨基丁酸（GABA）的浓度，这一点已得到充分证实。虽然关于GABA在人类促黄体生成素（LH）脉冲式分泌调控中的作用研究较少，但我们团队最近发现，在卵泡期晚期和黄体期中后期的正常女性中，服用丙戊酸盐对LH脉冲式分泌没有显著影响。然而，多项对大鼠的研究结果表明，GABA对LH分泌的调节可能取决于类固醇水平。这项研究的目的是确定长期服用丙戊酸钠是否会抑制去卵巢女性的LH脉冲式分泌。12名因非恶性肿瘤原因接受卵巢切除术的女性，每人在两个8小时的时间段内接受研究，每个时间段每隔5分钟采集一次血样。第一个时间段为对照期；第二个时间段，在前七天每8小时服用400毫克丙戊酸钠，并在研究当天的08:00和14:00服用。通过复极化荧光分光光度法测定血清丙戊酸盐，通过放射免疫分析法测定LH、雌二醇和孕酮。对血清LH序列进行去卷积程序，以重建垂体LH分泌模式。作者采用非参数方法识别LH脉冲。比较对照期和服用丙戊酸盐后的结果，包括脉冲数、脉冲持续时间、每个脉冲分泌的LH量、脉冲间期和平均血清LH水平。在所考虑的任何变量中，对照期和服用丙戊酸盐后的结果之间均无统计学显著差异。结论是，持续的血清丙戊酸盐水平不会改变去卵巢女性LH的脉冲式分泌。这意味着，在人类中，GABA可能不是GnRH脉冲发生器调节的决定性因素。
