Both estrogen receptor-α and -β are required for sexual differentiation of the anteroventral periventricular area in mice
Both estrogen receptor-α and -β are required for sexual differentiation of the anteroventral periventricular area in mice
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DOI：
10.1210/en.2005-0834
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Rissman, EF
中科院分区：
文献类型：
--
作者：
Bodo, C;Kudwa, AE;Rissman, EF
在围产期，下丘脑中的性二态性在几种情况下通过雄激素局部芳构化为雌激素来介导。在这一系列的实验中，两个雌激素受体（ER），ER α和ER β，在前腹侧脑室周围区（AVPV）的多巴胺能神经元的性二态亚群的分化的贡献进行了检查。在第一个实验中，测量了雌激素受体β敲除小鼠和野生型（WT）小鼠中两种性别的酪氨酸羟化酶（TH）免疫反应（-ir）AVPV神经元的数量。在第二个实验中，计算两种性别的ER α敲除、ER β敲除、双ER敲除和WT小鼠中AVPV内侧部分中TH-免疫阳性神经元的平均数量。在这两个实验中，TH-免疫反应细胞的数量是两性异形的预期，更多的TH-免疫反应神经元比野生型男性。有趣的是，所有敲除雄性动物中TH-免疫阳性神经元的平均数量显著高于WT雄性同窝仔。事实上，所有基因敲除雄性中的TH-ir细胞数量与雌性相当。在最后的实验中，C57 BL/6 J雌性小鼠在出生后的前3天内用雌二醇或两种ER之一的特异性激动剂处理。其他雄性和雌性幼仔接受溶媒注射。雌二醇或ER特异性激动剂治疗显著减少了女性大脑中TH-ir AVPV神经元的数量。我们的数据表明，ER α和ER β都参与了小鼠AVPV的性分化。
Sexual dimorphisms in the hypothalamus are mediated in several cases by local aromatization of androgens to estrogens during the perinatal period. In this series of experiments, the contributions of the two estrogen receptors (ERs), ER alpha and ER beta, to the differentiation of the sexually dimorphic subpopulation of dopaminergic neurons in the anteroventral periventricular area (AVPV) was examined. In the first experiment, numbers of tyrosine hydroxylase (TH) immunoreactive (-ir) AVPV neurons in ER beta knockout and wild- type (WT) mice of both sexes were measured. In the second experiment, the average number of TH-ir neurons in the medial portion of the AVPV in ER alpha knockout, ER beta knockout, double-ER knockout, and WT mice of both sexes was calculated. In both experiments TH-ir cell numbers were sexually dimorphic as expected, more TH-ir neurons than WT males. Interestingly the average number of TH-ir neurons in all knockout males was significantly higher than in WT male littermates. In fact, TH-ir cell numbers in all knockout males were equivalent to females. In a final experiment, C57BL/6J female mice were treated during the first 3 postnatal days with either estradiol, or a specific agonist for one of the two ERs. Additional male and female pups received vehicle injections. Treatments with estradiol or either ER-specific agonist significantly reduced the number of TH-ir AVPV neurons in female brains. Our data demonstrate that both ER alpha and ER beta are involved in the sexual differentiation of the AVPV in mice.