Brawer J R, Beaudet A, Desjardins G C, Schipper H M
Department of Anatomy, McGill University, Faculty of Medicine, Montreal, Quebec, Canada.
Biol Reprod. 1993 Oct;49(4):647-52. doi: 10.1095/biolreprod49.4.647.
Estradiol provides physiological signals to the brain throughout life that are indispensable for the development and regulation of reproductive function. In addition to its multiple physiological actions, we have shown that estradiol is also selectively cytotoxic to beta-endorphin neurons in the hypothalamic arcuate nucleus. The mechanism underlying this neurotoxic action appears to involve the conversion of estradiol to catechol estrogen and subsequent oxidation to o-semiquinone free radicals. The estradiol-induced loss of beta-endorphin neurons engenders a compensatory increment in mu opioid binding in the medial preoptic area rendering this region supersensitive to residual beta-endorphin or to other endogenous opioids. The consequent persistent opioid inhibition results in a cascade of neuroendocrine deficits that are ultimately expressed as a chronically attenuated plasma LH pattern to which the ovaries respond by becoming anovulatory and polycystic. This neurotoxic action of estradiol may contribute to a number of reproductive disorders in humans and in animals in which aberrant hypothalamic function is a major component.
雌二醇在整个生命过程中向大脑提供生理信号，这些信号对于生殖功能的发育和调节是不可或缺的。除了其多种生理作用外，我们还表明，雌二醇对下丘脑弓状核中的β-内啡肽神经元具有选择性细胞毒性。这种神经毒性作用的潜在机制似乎涉及雌二醇向儿茶酚雌激素的转化以及随后氧化为邻半醌自由基。雌二醇诱导的β-内啡肽神经元丧失导致内侧视前区μ阿片受体结合的代偿性增加，使该区域对残留的β-内啡肽或其他内源性阿片类物质超敏感。随之而来的持续阿片类物质抑制导致一系列神经内分泌缺陷，最终表现为血浆促黄体生成素（LH）模式长期减弱，卵巢对此的反应是无排卵和多囊性。雌二醇的这种神经毒性作用可能导致人类和动物的许多生殖障碍，其中异常的下丘脑功能是一个主要因素。
