Mello N K, Mendelson J H, Drieze J, Kelly M
Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, Belmont, Massachusetts 02178.
Neuropsychopharmacology. 1992 Dec;7(4):305-16.
Anovulation is a frequent concomitant of alcohol abuse, but it has been difficult to assess the acute effects of alcohol on ovulation. Estradiol benzoate (E2 beta) can stimulate a luteinizing hormone (LH) surge in ovariectomized monkeys that appears to be associated with increased luteinizing hormone-releasing hormone (LHRH) pulse frequency and amplitude. The acute effects of alcohol (2.5 and 3.5 g/kg) and an isocaloric sucrose control solution on LH and follicle-stimulating hormone (FSH) secretory activity were studied in five ovariectomized monkeys 41 to 51 hours after administration of E2 beta (42 micrograms/kg, IM). Integrated plasma samples were collected at 20-minute intervals over 10 hours. Under sucrose control conditions, LH increased to 445 and 584 ng/ml within 46 to 49.3 hours after E2 beta administration in two monkeys and high-amplitude LH pulses were evident in three monkeys. Alcohol (2.5 and 3.5 g/kg) significantly decreased the number of LH peaks and valleys (p < 0.01). Peak blood alcohol levels averaged 195 and 291 mg/dl. After 2.5 g/kg alcohol, there was no LH surge or LH pulses in four of five monkeys. A delayed LH surge occurred in one monkey 48 to 50.6 hours after E2 beta when blood alcohol levels decreased to 62 mg/dl. After 3.5 g/kg alcohol, no monkey had an LH surge and pulsatile LH release was significantly reduced in comparison to control conditions (p < 0.01). FSH levels remained stable across alcohol and control conditions. These data suggest that alcohol attenuates pituitary release of LH in response to E2 beta stimulation. These findings are consistent with menstrual cycle disruptions observed in alcohol-dependent women, social drinkers, and in a primate model of alcoholism.
无排卵是酒精滥用常见的伴随症状,但一直难以评估酒精对排卵的急性影响。苯甲酸雌二醇(E2β)可刺激卵巢切除的猴子出现促黄体生成素(LH)高峰,这似乎与促黄体生成素释放激素(LHRH)脉冲频率和幅度增加有关。在给五只卵巢切除的猴子注射E2β(42微克/千克,肌肉注射)后41至51小时,研究了酒精(2.5克/千克和3.5克/千克)和等热量蔗糖对照溶液对LH和促卵泡激素(FSH)分泌活性的急性影响。在10小时内每隔20分钟采集一次综合血浆样本。在蔗糖对照条件下,两只猴子在注射E2β后46至49.3小时内LH分别升至445和584纳克/毫升,三只猴子出现高幅度LH脉冲。酒精(2.5克/千克和3.5克/千克)显著减少了LH峰谷数量(p<0.01)。血液酒精峰值平均为195和291毫克/分升。在给予2.5克/千克酒精后,五只猴子中有四只未出现LH高峰或LH脉冲。一只猴子在E2β注射后48至50.6小时出现延迟的LH高峰,此时血液酒精水平降至62毫克/分升。在给予3.5克/千克酒精后,没有猴子出现LH高峰,与对照条件相比,LH的脉冲式释放显著减少(p<0.01)。在酒精和对照条件下,FSH水平保持稳定。这些数据表明,酒精会减弱垂体对E2β刺激的LH释放反应。这些发现与酒精依赖女性、社交饮酒者以及酒精中毒灵长类动物模型中观察到的月经周期紊乱一致。