Genetic basis of gonadal steroid-independent male social behavior

描述(由申请人提供)：这项建议的首要目的是增加我们对调节男性社会行为的遗传机制的理解。我们关于社会行为的大部分知识都是基于经典的工作，其中描述了类固醇激素和行为之间的关系：在大多数实验啮齿动物和野生哺乳动物中，男性的社会行为发生在繁殖季节，并且高度依赖性腺类固醇的同时可用。然而，在个体之间和跨物种之间，类固醇对男性社会行为的依赖是高度可变的，我们缺乏关于这些行为的遗传基础的知识仍然是理解通常被认为依赖性腺类固醇的人类男性行为的主要障碍。为了研究这一点，所使用的模式物种将是杂交的B6D2F1雄性小鼠，其中很大一部分小鼠在切除后很长一段时间内保留了完整的雄性社交和交配行为。我们已经完成了基因表达阵列的生物信息学分析，比较了已知的介导男性社会行为的关键部位、视前内侧区域和终纹床核的mRNA，在持续存在的杂交小鼠和那些在兰花切除后停止社交互动的小鼠之间进行比较。我们的分析将6个新的候选基因与复杂的社会行为联系起来。这项建议的具体目的是验证微阵列分析的结果，然后测试候选基因在性腺类固醇非依赖性男性社会行为中的作用。 项目简介：社会关系对所有年龄段的人的生活质量都很重要，尤其是在老年人和患者群体中。将从这项研究中受益的特定群体包括睾酮浓度下降的老年男性和前列腺癌幸存者，尽管他们接受了新的放射和手术治疗，并引入了西地那非，但绝大多数人表示对亲密关系的质量感到不满。我们希望，这项研究最终可能在不久的将来被用于开发治疗男性勃起功能障碍的新疗法。

DESCRIPTION (provided by applicant): The overriding aim of this proposal is to increase our understanding of the genetic mechanisms regulating male social behaviors. Most of our knowledge concerning social behavior has been based on classic work in which the relationship between the steroid hormones and behaviors were delineated: in most laboratory rodent species and mammals in the wild, male social behavior occurs during the breeding season and is highly dependent upon the concurrent availability of gonadal steroids. However, between individuals and across species, the dependence of steroids in male social behavior is highly variable, and our lack of knowledge concerning the genetic underpinnings of these behaviors remains a major obstacle to understanding human male behaviors normally thought to be dependent on gonadal steroids. To investigate this, the model species used will be hybrid B6D2F1 male mice in which a large proportion retains the complete repertoire of male social and copulatory behaviors long after orchidectomy. We have completed a bioinformatic analysis of gene expression arrays comparing mRNA from critical sites known to mediate male social behavior, the medial preoptic area and the bed nucleus of the stria terminalis, between hybrid mice that persist and those that cease to interact socially after orchidectomy. Our analysis has linked six novel candidate genes to complex social behaviors. The specific aims of this proposal are to validate the results of microarray analysis and then test the role of the candidate genes in gonadal steroid-independent male social behavior. Project Narrative: Social relationships are important for quality of life for people at all ages, but especially in senior citizens and patient populations. Specific groups that would benefit from this research include aging men experiencing declining testosterone concentrations and prostate cancer survivors that, despite new radiation and surgical treatments and the introduction of sildenafil, the vast majority report dissatisfaction with the quality of their intimate relationships. It is our hope that this research may ultimately be utilized in the near future to develop new treatments for erectile dysfunction in men.