The aromatase knockout (ArKO) mouse provides new evidence that estrogens are required for the development of the female brain
The aromatase knockout (ArKO) mouse provides new evidence that estrogens are required for the development of the female brain
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DOI：
10.1196/annals.1286.024
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Balthazart, J
中科院分区：
文献类型：
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作者：
Bakker, J;Honda, S;Balthazart, J
性别分化的经典观点是，男性大脑在睾丸分泌物的影响下发育，而女性大脑在没有任何激素刺激的情况下发育。然而，一些研究表明雌二醇在女性神经发育中可能发挥作用，尽管它们没有提供明确的证据表明雌二醇对女性大脑和行为的发育是不可或缺的。结果，由于缺乏合适的动物模型来测试雌激素对女性分化的可能贡献，这一假设随后被搁置。最近引进的芳香酶敲除（ArKO）小鼠，这是缺乏芳香酶活性，因为有针对性的突变在CYP19基因，因此不能芳香化雄激素雌激素，提供了一个新的机会，重新辩论雌二醇是否有助于女性大脑的发展。雌性ArKO小鼠在成年后用雌二醇和孕酮治疗后表现出前凸行为水平降低，表明雌二醇是控制雌性小鼠这种行为的神经机制发育所必需的。受影响的神经系统可能包括嗅觉系统，因为ArKO女性在同种气味的嗅觉调查中也表现出损伤。因此，性别分化的经典观点，即女性大脑在没有任何激素分泌的情况下发育，需要重新审视。
The classic view of sexual differentiation is that the male brain develops under the influence of testicular secretions, whereas the female brain develops in the absence of any hormonal stimulation. However, several studies have suggested a possible role of estradiol in female neural development, although they did not provide unequivocal evidence that estradiol is indispensable for the development of the female brain and behavior. As a result, the hypothesis subsequently languished because of the lack of a suitable animal model to test estrogen's possible contribution to female differentiation. The recent introduction of the aromatase knockout (ArKO) mouse, which is deficient in aromatase activity because of a targeted mutation in the CYP19 gene and therefore cannot aromatize androgen to estrogen, has provided a new opportunity to reopen the debate of whether estradiol contributes to the development of the female brain. Female ArKO mice showed reduced levels of lordosis behavior after adult treatment with estradiol and progesterone, suggesting that estradiol is required for the development of the neural mechanisms controlling this behavior in female mice. The neural systems affected may include the olfactory systems in that ArKO females also showed impairments in olfactory investigation of odors from conspecifics. Thus, the classic view of sexual differentiation, that is, the female brain develops in the absence of any hormonal secretion, needs to be re-examined.