Coumestrol antagonizes neuroendocrine actions of estrogen via the estrogen receptor α
Coumestrol antagonizes neuroendocrine actions of estrogen via the estrogen receptor α
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DOI：
10.1177/153537020122600406
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发表时间：
2001-04-01
影响因子：
3.2
通讯作者：
Rissman, EF
中科院分区：
文献类型：
--
作者：
Jacob, DA;Temple, JL;Rissman, EF
植物雌激素香豆雌酚对外周生殖组织具有雌激素样作用。然而，在大脑中，这种化合物具有雌激素和抗雌激素作用。我们使用雌激素受体a敲除小鼠（ER α KO）来确定香豆雌酚是否在小鼠中具有雌激素作用，以及这些作用是否由经典的ER α介导。将雌性野生型（WT）和ERaKO小鼠卵巢切除并用雌二醇（E-2）、膳食香豆雌酚、两者或不用化合物处理。10天后，处死动物，采集血液，灌注脑组织，将固定的脑切片，采用免疫细胞化学方法定量测定下丘脑内侧视前核（POA）和腹内侧核（VMN）中的孕酮受体（PR）。测定血浆中的促黄体生成激素（LH），雌激素处理诱导WS雌性动物脑中两个区域的PR免疫反应性。在ER α KO小鼠中，诱导较低水平的PR。通过与香豆雌酚共同处理，在POA中E-2对PR的刺激作用减弱，在VMN中观察到相同的趋势，用E-2处理的WT卵巢切除雌性动物具有低水平的LH，尽管LH在未处理的雌性中是高的，并且在用香豆雌酚处理的切除卵巢的雌性中甚至更高，但所有处理组中的ER α KO雌性具有高水平的LH。总之，结果表明香豆雌酚在脑和垂体中具有抗雌激素作用，并且ER α介导这些作用。
The phytoestrogen coumestrol has estrogenic actions on peripheral reproductive tissues. Yet in the brain this compound has both estrogenic and anti-estrogenic effects. We used estrogen receptor a knockout mice (ER alpha KO) to determine whether coumestrol has estrogenic actions in mice and also if these effects are mediated by the classic ER alpha. Female wild-type (WT) and ERaKO mice were ovariectomized and treated with estradiol (E-2), dietary coumestrol, both, or neither compound. Ten days later the animals were sacrificed, blood was collected, and brain tissues were perfused, Fixed brains were sectioned and immunocytochemistry was employed to quantify progesterone receptors (PR) in the medial preoptic (POA) and ventromedial nucleus of the hypothalamus (VMN). Plasma was assayed for luteinizing hormone (LH), Estrogen treatment induced PR immunoreactivity in both regions in brains of WS females, In ER alpha KO mice, lower levels of PR were induced, The stimulatory effects of E-2 on PR were attenuated in the POA by cotreatment with coumestrol, and the same trend was noted in the VMN, WT ovariectomized females treated with E-2 had low levels of LH, while LH was high in untreated females and even higher in ovariectomized females treated with coumestrol, ER alpha KO females in all treatment groups had high levels of LH, Taken together, the results show that coumestrol has anti-estrogenic actions in the brain and pituitary and that ER alpha mediates these effects.