Genetic basis of gonadal steroid-independent male social behavior

性腺类固醇独立的男性社会行为的遗传基础

• 批准号: 7621037
• 负责人: Jin Ho Park
• 金额: $ 8.95万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-07 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7621037
• 关键词: Age; Alleles; Antiandrogen Therapy; Behavior; Behavioral; Behavioral Genetics; Bioinformatics; Brain region; Breeding; Cancer Patient; Cancer Survivor; Candidate Disease Gene; Complex; Copulation; Dependence; Elderly; Erectile dysfunction; Face; Future; Gene Expression; Genes; Genetic; Goals; Gonadal Steroid Hormones; Gonadal structure; Hormonal; Hybrids; Immunofluorescence Immunologic; Inbred Mouse; Individual; Individual Differences; Knowledge; Label; Laboratories; Libido; Link; Malignant neoplasm of prostate; Mammals; Medial; Mediating; Messenger RNA; Microarray Analysis; Modeling; Molecular Genetics; Mus; Operative Surgical Procedures; Orchiectomy; Partner in relationship; Play; Preoptic Areas; Proteins; Quality of life; Radiation; Recombinants; Reporting; Reproductive Behavior; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; Seasons; Sex Behavior; Sexual Dysfunction; Site; Social Behavior; Structure of terminal stria nuclei of preoptic region; Testing; Testosterone; Western Blotting; Work; base; deviant; experience; human male; improved; interest; intimate behavior; male; men; men' s group; mouse model; novel; patient population; programs; response; sildenafil; social; steroid dependence; steroid hormone

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.

描述（由申请人提供）：本提案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。我们对社会行为的大部分了解都是基于经典的研究，其中描述了类固醇激素和行为之间的关系：在大多数实验室啮齿动物和野生哺乳动物中，雄性社会行为发生在繁殖季节，并且高度依赖于性腺类固醇的同时可用性。然而，在个体之间和跨物种之间，类固醇在男性社会行为中的依赖性是高度可变的，并且我们缺乏关于这些行为的遗传基础的知识仍然是理解人类男性行为的主要障碍，通常认为这些行为依赖于性腺类固醇。为了研究这一点，所用的模型种属将是杂交B6D2F1雄性小鼠，其中大部分小鼠在睾丸切除后很长时间内保留了雄性社会和交配行为的完整谱系。我们已经完成了对基因表达阵列的生物信息学分析，比较了持续存在的杂交小鼠和停止社交互动的杂交小鼠之间已知介导雄性社会行为的关键位点（内侧视前区和终纹床核）的mRNA。睾丸切除术。我们的分析将六个新的候选基因与复杂的社会行为联系起来。该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。 项目叙述：社会关系对所有年龄段的人的生活质量都很重要，尤其是老年人和患者群体。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，尽管有新的放射和手术治疗以及西地那非的引入，但绝大多数人对他们的亲密关系质量表示不满。我们希望这项研究最终可以在不久的将来用于开发男性勃起功能障碍的新疗法。