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【bio-news】不育新病因：大脑中雌激素信号途径的
There are many causes of infertility. The fact that nerve cells can also play a role is little known. The hormone estrogen regulates the activity of neurons that give the starting signal for ovulation. Collaborating with international research groups, scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have studied this signaling pathway in detail and have discovered new causes of infertility.
很多原因可以导致不育，但很少有人知道神经细胞也起到一定作用。雌激素调节神经细胞活动，发送排卵信号。德国癌症研究中心的研究人员与其他研究组合作，详细研究了这一信号转导途径，发现了不育的新机制。
The time of a woman’s monthly ovulation depends on how far the egg is matured and on the brain being informed about this. Estrogen, a hormone produced in the ovaries, transmits this message to the brain around the 14th day of the fertility cycle. In response, the stimulated neurons trigger increased release of another hormone called gonadotropin from the pituitary gland and, thus, give the signal for ovulation.
女性每月的排卵时间由卵泡成熟程度及大脑对此的反应决定。雌激素由卵巢分泌，在月经周期第十四天将卵泡成熟信息传至大脑，受刺激的神经细胞促使垂体释放促性腺激素分泌增加，然后发出排卵指令。
“The better we understand how estrogens work and what may go wrong in the interaction with neurons, the more possibilities we will have to counteract infertility,” says Professor Günther Schütz, head of the Division of Molecular Biology of the Cell I at the German Cancer Research Center. Schütz and his co-workers, collaborating with Professor Allan Herbison in New Zealand and two research groups in the U.S., demonstrated that only a specific group of neurons in the brain receive the hormone signal. These cells need to have the estrogen receptor alpha in order to recognize the message and subsequently trigger production of the necessary sex hormones.
德国癌症研究中心分子系主任、Günther Schütz教授说：“我们对雌激素如何作用及它与神经细胞反应时会出现的问题理解越深，就越有可能攻克不育。”Günther及其同事与新西兰的Allan Herbison教授及美国两个研究组合作，阐明了脑内只有一组特定神经细胞可以接收到这一激素信号。这些细胞必须具备雌激素受体α来识别信号，并随后触发必要的性激素释放。
Estrogen receptors are specialized on perceiving the estrogen hormone. Two types of estrogen receptors, alpha and beta, are found in the nervous system. It has been known that female animals suffer from lesions in the ovaries, mammary glands and uterus when they lack the estrogen receptor alpha. “Every single one of these defects is sufficient to make the animals infertile,” says biochemist Dr. Tim Wintermantel. Moreover, there were indications suggesting that estrogen receptor beta is also relevant for fertility. The scientists performed several experiments to find out more about the role played by the two estrogen receptors in the activation of neurons in the brain.
神经系统中存在ɑ及β两种雌激素受体，它们特异性识别雌激素。雌性动物雌激素受体ɑ缺乏时，会发生卵巢、乳腺及子宫功能障碍，生化学家Tim Wintermantel教授说，其中任何一种原因都可以导致不育。此外，有证据表明，雌激素受体β也与不育有关。研究人员进行了一系列实验，以探讨这两种雌激素受体在脑细胞激活中所起的作用。
They studied mice who lacked the estrogen receptor alpha only in nerve cells. Additional estrogen given to these animals failed to trigger the hormone signal for ovulation. Furthermore, the investigators administered synthetic molecules developed and provided by Schering AG, Berlin, to healthy female mice. These substances activated exclusively the estrogen receptor alpha. This alone was sufficient to increase hormone production substantially. “Both experiments led to corresponding results,”. “The estrogen receptor alpha needs to be not only present but also activated.”
神经细胞中单纯缺乏雌激素受体ɑ的老鼠，即使给予过量的雌激素也不能引起排卵信号。健康雌鼠注入Schering AG开发并提供的能特异性激活雌激素受体ɑ的复合物后，激素分泌增加。 Tim Wintermantel解释“两个实验结果一致，说明仅有雌激素受体还不够，它必须被激活。”
Nevertheless, a gap in the researchers’ model became apparent: The neurons that are critical for the release of the messenger substance gonadotropin do not have the estrogen receptor alpha. How do the gonadotropin producers receive the signal to increase hormone release if they are unable to receive the estrogen message? The researchers discovered that a second group of neurons in the hypothalamus transmits the message. They demonstrated that these mediators are equipped with the alpha antenna and that they use long cellular extensions to connect with the cells that induce gonadotropin production in the pituitary gland.
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作者:admin@医学,生命科学 2011-06-29 18:20
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