Kudwa A E, Harada N, Honda S-I, Rissman E F
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
Physiol Behav. 2009 May 25;97(2):146-50. doi: 10.1016/j.physbeh.2009.02.023. Epub 2009 Feb 28.
Exposure to estrogens during critical developmental periods and in adulthood affects sex differences in the brain. We examined the roles of estradiol (E2) and phytoestrogens, and their interactions, on potential sex differences in brain. We used aromatase knockout (ArKO) mice, which cannot produce endogenous estrogens, along with wild type (WT) littermates. Mice were gestated, raised and maintained on a diet either rich in phytoestrogens or a diet virtually void of soy-derived phytoestrogens. Adult males and females were gonadectomized and received implants filled with 17-beta-estradiol to induce progestin receptors (PR), while controls received empty implants. Mice were sacrificed five days later and brain sections containing the posterodorsal medial amygdala (MePD) were processed for PR immunoreactivity. Activation of sex differences in PR required adult E2 treatment. A diet high in phytoestrogens was required for expression of sex differences in PR after E2 treatment. Our data underscore the important contribution of dietary phytoestrogens for the development of sex differences in PR-ir in the adult mouse medial amygdala. We hypothesize that both aromatization of androgens to estrogens and dietary sources of additional estrogens are part of the normal requirement for sex differences in the rodent brain.
在关键发育时期和成年期接触雌激素会影响大脑的性别差异。我们研究了雌二醇（E2）和植物雌激素及其相互作用对大脑潜在性别差异的作用。我们使用了不能产生内源性雌激素的芳香化酶敲除（ArKO）小鼠，以及野生型（WT）同窝小鼠。小鼠在富含植物雌激素的饮食或几乎不含大豆衍生植物雌激素的饮食中妊娠、饲养和维持。成年雄性和雌性小鼠进行性腺切除，并接受填充有17-β-雌二醇的植入物以诱导孕激素受体（PR），而对照组接受空植入物。五天后处死小鼠，对含有后内侧杏仁核（MePD）的脑切片进行PR免疫反应性处理。PR性别差异的激活需要成年期E2处理。E2处理后，PR性别差异的表达需要高植物雌激素饮食。我们的数据强调了饮食中的植物雌激素对成年小鼠内侧杏仁核PR免疫反应性性别差异发展的重要贡献。我们假设雄激素向雌激素的芳香化以及额外雌激素的饮食来源都是啮齿动物大脑性别差异正常需求的一部分。
