Roles of Estrogen Receptor-α Gene Expression in Reproduction-Related Behaviors in Female Mice* * This work was supported by the Harry Frank Guggenheim Foundation (to S.O.), the University of Missouri-Columbia molecular biology program (to D.B.L.), and NIH Grant HD-05751 (to D.W.P.).-猫眼课题宝

雌激素受体-α 基因表达在雌性小鼠生殖相关行为中的作用* * 这项工作得到了 Harry Frank Guggenheim 基金会（S.O.）、密苏里大学哥伦比亚分校分子生物学项目（D.B.L.）和 NIH 的支持

DOI：

发表时间：

1998

期刊：

Endocrinology

影响因子：

4.8

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

S. Ogawa;Vincent Eng;Julia A. Taylor;D. Lubahn;K. Korach;D. Pfaff

在雌激素受体基因敲除（ERKO）小鼠中研究了雌激素受体β型（ER β）基因表达在雌性生殖行为调节中的作用。雌激素或雌激素加炔雌醇治疗的性腺切除ERKO小鼠未显示任何脊柱前凸反应。详细的行为分析显示，ERKO女性也缺乏性行为的互动前凸反应。他们非常排斥雄性小鼠的尝试坐骑，因为它们不能表现出任何插入。在居民入侵者的侵略测试，性腺完整的ERKO女性更积极的对女性入侵者小鼠比野生型（WT）小鼠。性腺切除术并没有影响攻击行为的水平，以及它们的基因型差异，当小鼠在性腺切除术前后进行测试。然而，当小鼠在性腺切除术后第一次进行测试时，很少有ERKO小鼠表现出攻击性。与侵略相反，男性型的性行为表现出的居民小鼠对女性入侵者小鼠在侵略测试中是没有什么不同的ERKO和WT小鼠，并完全废除后，性腺切除术的居民小鼠。最后，还发现ERKO雌性动物对放在它们家笼中的新生幼崽表现出极大降低的父母行为水平。这些父母行为的变化不受性腺切除术的影响。与野生型（WT）或杂合型（HZ）同窝仔相比，ERKO雌性动物在性腺完整或性腺切除后20 - 65天进行检测时，获得的幼仔数量显著较少，且幼仔寿命较长。此外，在亲代行为测试期间，与WT和HZ小鼠相比，ERKO小鼠表现出杀雄剂的百分比显著更高，WT和HZ小鼠很少表现出杀雄剂。总之，这些发现表明ER β基因表达在雌性小鼠中起着关键作用，不仅对性行为，而且对其他相关行为，如父母和攻击行为。此外，持续存在的基因型差异，在父母和攻击性行为后，性腺切除表明，ER β激活神经发育过程中也可能参与这些行为的调节。它是很好地建立了卵巢类固醇，雌激素，调节女性生殖和脊柱前凸的行为，结合细胞内雌激素受体（ER）在大脑中。雌激素的这种基因组作用被认为不仅通过经典形式的ER（现在称为ER β）介导，而且还可能通过最近克隆的第二种形式的ER，ER β介导（1，2）。最近的研究表明...

The role of gene expression of the estrogen receptor-␣ form (ER␣) in the regulation of female reproductive behavior was investigated in estrogen receptor knockout (ERKO) mice, deficient specifically for the ER␣, but not the ER␤, gene. Estrogen-or estrogen-plus progesterone-treated gonadectomized ERKO mice did not show any lordosis response. Detailed behavioral analysis revealed that ERKO females were also deficient in sexual behavioral interactions preceding the lordosis response. They were extremely rejective toward attempted mounts by stud male mice, which could not show any intromissions. During resident-intruder aggression tests, gonadally intact ERKO females were more aggressive toward female intruder mice than wild-type (WT) mice. Gonadectomy did not influence the levels of aggressive behavior, and their genotype differences when mice were tested both before and after gonadectomy. However, when mice were tested after gonadectomy for the first time, very few ERKO mice showed aggression. In contrast to aggression, male-type sexual behavior shown by resident mice toward female intruder mice during aggression tests was not different between ERKO and WT mice and was completely abolished after gonadectomy of the resident mice. Finally, it was also found that ERKO females showed greatly reduced levels of parental behavior toward newborn pups placed in their home cage. These changes in parental behavior were not influenced by gonad-ectomy. ERKO females retrieved significantly fewer numbers of pups with longer latencies compared with wild-type (WT) or heterozygous (HZ) littermates when they were tested as gonadally intact or 20 – 65 days after gonadectomy. In addition, during parental behavior tests, a significantly higher percentage of ERKO mice exhibited infanticide compared with WT and HZ mice, which rarely showed infanticide. Taken together, these findings suggest that ER␣ gene expression plays a key role in female mice, not only for sexual behavior but also for other interrelated behaviors, such as parental and aggressive behaviors. In addition, persistence of genotype differences in parental and aggressive behavior after gonadectomy indicates that ER␣ activation during neural developmental processes may also be involved in the regulation of these behaviors. I T IS WELL established that the ovarian steroid, estrogen, regulates female reproduction and lordosis behavior by binding to intracellular estrogen receptors (ER) in the brain. This genomic action of estrogen is assumed to be mediated not only through the classical form of ER (now termed ER␣), but also possibly through the second form of ER, ER␤, which was recently cloned (1, 2). Recent studies have shown that …