McGarvey C, Cates P A, Brooks A, Swanson I A, Milligan S R, Coen C W, O'Byrne K T
Division of Anatomy, Cell and Human Biology, Division of Physiology, GKT School of Biomedical Sciences, King's College London, Guy's Campus, London, United Kingdom SE1 1UL.
Endocrinology. 2001 Mar;142(3):1202-8. doi: 10.1210/endo.142.3.8015.
Phytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans. The aims of this study were 2-fold: 1) to determine in vivo whether genistein and coumestrol act on the GnRH pulse generator to suppress hypothalamic multiunit electrical activity volleys and associated LH pulses and/or on the pituitary to suppress the LH response to GnRH; and 2) to examine the effect of these phytoestrogens on GnRH-induced pituitary LH release in vitro and to determine whether estrogen receptors are involved. Wistar rats were ovariectomized and chronically implanted with recording electrodes and/or indwelling cardiac catheters, and blood samples were taken every 5 min for 7--11 h. Intravenous infusion of coumestrol (1.6-mg bolus followed by 2.4 mg/h for 8.5 h) resulted in a profound inhibition of pulsatile LH secretion, a 50% reduction in the frequency of hypothalamic multiunit electrical activity volleys, and a complete suppression of the LH response to exogenous GnRH. In contrast, both genistein (1.6-mg bolus followed by 2.4 mg/h for 8.5 h) and vehicle were without effect on pulsatile LH secretion. Coumestrol (10(-5) M; over 2 or 4 h) suppressed GnRH-induced pituitary LH release in vitro, an effect blocked by the antiestrogen ICI 182,780. It is concluded that coumestrol acts centrally to reduce the frequency of the hypothalamic GnRH pulse generator. In addition, the inhibitory effects of coumestrol on LH pulses occur at the level of the pituitary by reducing responsiveness to GnRH via an estrogen receptor-mediated process.
植物雌激素可对动物和人类的促性腺激素分泌产生抑制作用。本研究的目的有两个：1）在体内确定金雀异黄素和香豆雌酚是否作用于GnRH脉冲发生器以抑制下丘脑多单位电活动群集及相关的LH脉冲，和/或作用于垂体以抑制LH对GnRH的反应；2）研究这些植物雌激素对体外GnRH诱导的垂体LH释放的影响，并确定雌激素受体是否参与其中。将Wistar大鼠去卵巢，并长期植入记录电极和/或留置心脏导管，每5分钟采集一次血样，共采集7 - 11小时。静脉输注香豆雌酚（1.6毫克推注，随后以2.4毫克/小时的速度输注8.5小时）导致LH脉冲分泌受到显著抑制，下丘脑多单位电活动群集频率降低50%，并且完全抑制了LH对外源性GnRH的反应。相比之下，金雀异黄素（1.6毫克推注，随后以2.4毫克/小时的速度输注8.5小时）和溶剂对照均对LH脉冲分泌无影响。香豆雌酚（10⁻⁵ M；持续2或4小时）在体外抑制了GnRH诱导的垂体LH释放，该作用被抗雌激素ICI 182,780阻断。得出的结论是，香豆雌酚通过中枢作用降低下丘脑GnRH脉冲发生器的频率。此外，香豆雌酚对LH脉冲的抑制作用通过雌激素受体介导的过程降低垂体对GnRH的反应性而发生在垂体水平。
