Bäckström T, Gee K W, Lan N, Sörensen M, Wahlström G
Department of Gynecology, University of Umeå, Sweden.
Ciba Found Symp. 1990;153:225-30; discussion 230-9. doi: 10.1002/9780470513989.ch13.
Increasing numbers of reports indicate direct effects of ovarian steroids on the central nervous system. Effects of progesterone and its metabolites on brain excitability in humans and in experimental animals have been studied. Anti-epileptic effects have been shown in cats and in women with partial epilepsy and well-defined epileptic foci. The reduced progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one and its 5 beta analogue also decreased the epileptic activity resulting from a penicillin-induced cortical focus in cats. 5 alpha-Pregnan-3 alpha-ol-20-one protected mice against metrazol-, bicuculline- and picrotoxin-induced seizures but not against electroshock-and strychnine-induced seizures. Progesterone, 5 alpha-pregnan-3 alpha-ol-20-one and 5 beta-pregnan-3 alpha-ol-20-one also induce anaesthesia in humans and animals; in a rat model of anaesthesia 5 alpha-pregnan-3 alpha-ol-20-one was eight times more potent than methohexitone (the most potent anaesthetic barbiturate). Anaesthesia with loss of the eyelash reflex was observed in humans 75-90 seconds after the intravenous injection of 5 beta-pregnan-3 alpha-ol-20-one in lipid emulsion. The in vivo production and brain distribution of centrally active steroids has also been studied in relation to the phases of the ovarian and menstrual cycle. A subset of women with epilepsy show changes in seizure frequency in relation to hormonal variations during the menstrual cycle. In the luteal phase when progesterone levels are high the number of generalized seizures is low. It is possible that progesterone and its metabolites play a role in epileptic seizures and also in the premenstrual syndrome.
越来越多的报告表明卵巢类固醇对中枢神经系统有直接影响。人们已经研究了孕酮及其代谢产物对人类和实验动物大脑兴奋性的影响。在猫以及患有部分性癫痫且癫痫病灶明确的女性中已显示出抗癫痫作用。孕酮代谢产物5α-孕烷-3α-醇-20-酮及其5β类似物也降低了猫青霉素诱导的皮质病灶所产生的癫痫活动。5α-孕烷-3α-醇-20-酮可保护小鼠免受戊四氮、荷包牡丹碱和印防己毒素诱导的惊厥，但不能保护其免受电休克和士的宁诱导的惊厥。孕酮、5α-孕烷-3α-醇-20-酮和5β-孕烷-3α-醇-20-酮在人类和动物中也会诱导麻醉；在大鼠麻醉模型中，5α-孕烷-3α-醇-20-酮的效力比甲己炔巴比妥（最有效的麻醉性巴比妥酸盐）强八倍。在静脉注射脂质乳剂中的5β-孕烷-3α-醇-20-酮后75至90秒，人类出现了伴有睫毛反射消失的麻醉状态。还研究了中枢活性类固醇在体内的产生及其在大脑中的分布与卵巢和月经周期各阶段的关系。一部分癫痫女性的癫痫发作频率会随月经周期中的激素变化而改变。在黄体期，孕酮水平较高时，全身性癫痫发作的次数较少。孕酮及其代谢产物可能在癫痫发作以及经前综合征中起作用。
