A previously uncharacterized role for estrogen receptor β:: Defeminization of male brain and behavior
A previously uncharacterized role for estrogen receptor β:: Defeminization of male brain and behavior
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DOI：
10.1073/pnas.0500752102
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发表时间：
2005-03-22
影响因子：
11.1
通讯作者：
Rissman, EF
中科院分区：
文献类型：
--
作者：
Kudwa, AE;Bodo, C;Rissman, EF
在有性繁殖的物种中，大脑和行为的性别差异是普遍存在的。两性异形的一个原因是性腺激素循环浓度的发育差异。新生儿睾丸产生雄激素；因此，雄性同时暴露于睾酮和雌二醇，而雌性直到青春期才暴露于高浓度的这两种激素。传统上，神经性别差异的发展是由雌二醇启动的，它激活了男性新生儿的两个过程；男性化是指男性行为的发展，而女性化是指丧失表现女性行为的能力。在这里，我们验证了去女性化是由雌激素受体（ER β）调节的假设。成年雄性ER β敲除小鼠和WT小鼠进行性腺切除术，用雌性启动激素治疗，并测试其接受行为。雄性ER β敲除小鼠与WT幼崽相比，表现出明显更高的雌性接受性，表明不完全去雌性化。无论基因型如何，睾丸完好的雄性在性行为的任何方面都没有差异。在嗅觉偏好测试中，两种基因型的雄性对雌性脏的被褥表现出相同的偏好。基于这些结果，我们假设内质网β参与了大脑和行为的去女性化。内质网β功能的这一方面可能会导致我们对基于神经的两性二态人类行为的理解的发展。
Sex differences in brain and behavior are ubiquitous in sexually reproducing species. One cause of sexual dimorphisms is developmental differences in circulating concentrations of gonadal steroids. Neonatal testes produce androgens; thus, males are exposed to both testosterone and estradiol, whereas females are not exposed to high concentrations of either hormone until puberty. Classically, the development of neural sex differences is initiated by estradiol, which activates two processes in male neonates; masculinization, the development of male-type behaviors, and defeminization, the loss of the ability to display female-type behaviors. Here, we test the hypothesis that defeminization is regulated by estrogen receptor beta (ER beta). Adult male ER beta knockout and WT mice were gonadectomized, treated with female priming hormones, and tested for receptive behavior. Indicative of incomplete defeminization, male ER beta knockout mice showed significantly higher levels of female receptivity as compared with WT littermates. Testes-intact males did not differ in any aspects of their male sexual behavior, regardless of genotype. In olfactory preference tests, males of both genotypes showed equivalent preferences for female-soiled bedding. Based on these results, we hypothesize that ER beta is involved in defeminization of brain and behavior. This aspect of ER beta function may lead to developments in our understanding of neural-based sexually dimorphic human behaviors.