Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action
Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action
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DOI：
10.1128/mcb.26.5.2012-2018.2006
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Szpirer, C
中科院分区：
文献类型：
--
作者：
De Mees, C;Laes, JF;Szpirer, C
先前已经表明，甲胎蛋白（AFP）无效等位基因纯合子的雌性小鼠由于无排卵而不育，这可能是由于下丘脑-垂体轴的缺陷。在这里，我们表明，这些雌性小鼠表现出特定的异常，在垂体中的许多基因的表达，包括参与促性腺激素释放激素途径，这是低表达的基因。在下丘脑中，促性腺激素释放激素基因Gnrh 1也被发现下调。然而，垂体基因表达可以正常化，生育能力可以通过使用芳香酶抑制剂阻断产前雌激素合成来挽救。这些结果表明，AFP保护发育中的女性大脑免受产前雌激素暴露的不利影响，并澄清了关于这种胎儿蛋白在大脑性别分化中的作用的长期争论。
It has been shown previously that female mice homozygous for an alpha-fetoprotein (AFP) null allele are sterile as a result of anovulation, probably due to a defect in the hypothalamic-pituitary axis. Here we show that these female mice exhibit specific anomalies in the expression of numerous genes in the pituitary, including genes involved in the gonadotropin-releasing hormone pathway, which are underexpressed. In the hypothalamus, the gonadotropin-releasing hormone gene, Gnrh1, was also found to be down-regulated. However, pituitary gene expression could be normalized and fertility could be rescued by blocking prenatal estrogen synthesis using an aromatase inhibitor. These results show that AFP protects the developing female brain from the adverse effects of prenatal estrogen exposure and clarify a long-running debate on the role of this fetal protein in brain sexual differentiation.