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NEUROENDOCRINE REGULATION OF AGGRESSIVE BEHAVIOR

攻击性行为的神经内分泌调节

基本信息

批准号：
3440834
负责人：
NEAL G SIMON
金额：
$ 5万
依托单位：
LEHIGH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-08-01 至 1989-09-30
项目状态：
已结题

项目摘要

The mechanisms through which testosterone (T) stimulates the display of male-typical aggressive behavior remain controversial. At the center of this issue is the necessity for defining the role of the androgenic and estrogenic metabolites of T in the promotion of fighting behavior. To address this fundamental question about hormone action in the central nervous system, a research strategy that integrated behavioral and biochemical studies of mice from a number of different strains was recently employed. Genotypic differences in responsiveness to the aggression-promoting property of androgen and estrogen were found among male mice from the CF-1, CFW, and CD-1 strains. These differences in sensitivity appeared to be related to genetically determined differences in receptor binding. More specifically, responsiveness to estrogen (as measured with diethylstilbestrol, DES) was related to either a higher number of binding sites or higher affinity binding between DES-estrogen receptor. The binding of DHT, an androgen that was moderately effective in promoting aggression in the 3 strains, was not systematically related to its behavioral effects. The goal of the proposed series of experiments will be to further explore the relationship between receptor binding and behavioral responsiveness through the use of integrated behavioral and biochemical investigations. The studies will determine whether the relationship between K/d, B/max, and sensitivity to the aggression-promoting property of DES can be extended to other estrogens and androgens or whether additional aspects of receptor binding (dissociation kinetics, nuclear binding) should be examined to identify the molecular correlates of behavioral responsiveness to these hormones. In addition, the role of neonatal hormonal stimulation is establishing the biochemical basis for behavioral responsiveness later in life will also be examined. The studies are expected to support the hypothesis of a relationship between receptor binding and responsiveness to the aggression-promoting property of androgen and estrogen. Such findings would significantly enhance our understanding of the molecular processes involved in the hormonal regulation of intermale aggressive behavior in mice and may facilitate the development of a theoretical model of steroid sensitivity in neural tissues that can be assessed in future investigations.

睾酮(T)刺激性激素分泌的机制男性典型的攻击性行为的表现仍然存在争议。这个问题的核心是有必要界定促性腺激素的雄激素代谢产物和雌激素代谢产物关于打斗行为的。要解决这一基本问题，激素在中枢神经系统中的作用，一种研究策略对小鼠的行为和生化综合研究最近使用了许多不同的菌株。遗传型对促进攻击性反应的差异在雄性小鼠中发现雄激素和雌激素的特性来自CF-1、CFW和CD-1菌株。这些差异体现在敏感度似乎与基因决定有关受体结合的差异。更具体地说，响应性与雌激素(用己烯雌酚测定)有关到更多的结合位点或更高的亲和力 DES-雌激素受体之间的结合。DHT、ANN的结合力在促进攻击性方面适度有效的雄激素在3个菌株中，与其行为没有系统的相关性效果。拟议的一系列实验的目标将是进一步探讨受体结合与行为的关系通过使用集成的行为和生化调查。这些研究将确定是否 K/d、B/max与灵敏度之间的关系 DES的攻击性可以推广到其他雌激素和雄激素还是受体的附加方面应检查结合(解离动力学、核结合) 确定行为反应的分子相关性这些荷尔蒙。此外，新生儿荷尔蒙的作用刺激是建立行为的生物化学基础在以后的生活中，我们也将考察他们的反应能力。预计这些研究将支持这样一种假设：受体结合与血管紧张素转换酶反应的关系雄激素和雌激素的促攻击性。是这样的这些发现将极大地增强我们对参与激素调节的分子过程小鼠的雄性间攻击行为，并可能促进神经内分泌激素敏感性理论模型的建立可以在未来的研究中评估的组织。