DIFFERENCES IN CCK RELEASE AND FUNCTION

CCK 释放和功能的差异

• 批准号: 3402141
• 负责人: PAUL E MICEVYCH
• 金额: $ 12.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3402141
• 关键词: androgens; autoradiography; cell parasexuality; cholecystokinin; cholesterol; colchicine; embryo /fetus; estradiol; estrogens; fluorescence microscopy; fluorescent dye /probe; histochemistry /cytochemistry; hormone regulation /control mechanism; immunochemistry; laboratory rat; limbic system; microinjections; neural information processing; neuroendocrine system; neuropeptides; newborn animals; ovariectomy; potassium; propionates; sex behavior; sex differentiation; sex hormones; steroid hormone biosynthesis; testosterone

The main objective of the present study is to elucidate the relationship between the gonadal steroid environment and the organization and function of a steroid-sensitive cholecystokinin (CCK) circuit which is part of a sexually dimorphic limbic- hypothalamic system. This interconnected system, including the medial amygdaloid nucleus, bed nucleus of the atria terminalis, medial preoptic nucleus and the ventromedial region of the hypothalamus, is implicated in the integration of sensory and sex steroid cues involved in the CNS control of reproductive behavior. The sexually dimorphic distribution of the neuroactive peptide CCK in the limbic-hypothalamic system appears to be an important chemical marker for the action of steroids, especially since in this system the mechanism of steroid-regulation of CCK synthesis in males may be different from that in females. Initially, we propose to characterize the interaction between gonadal steroids and the CCK circuit in adult males by determining the metabolite of testosterone necessary to maintain the limbic-hypothalamic CCK circuit. To examine the steroidal influence on CCK release, in vitro superfusion will be utilized. In order to obtain a morphological signature of steroidal action on CCK cells, a combination of steroid autoradiography and CCK- immunohistochemistry will be used to determine if CCK cells in the male concentrate steroids. To begin to elucidate the integration of steroid information within the limbic-hypothalamic system, retrograde tract-tracing will be combined with steroid autoradiography and immunohistochemistry. The role of CCK in the male limbic-hypothalamic system will be tested by injecting CCK into discrete loci in this system. Finally, to understand the organizing-role of gonadal steroids during development, a series of rats will have their perinatal sex-steroid environment altered to produce sex-reversed adults in terms of their reproductive behavior. In two parallel groups of rats, the distribution of CCK- positive cells in the limbic-hypothalamic system of these rats will be determined and correlated with the effects of CCK on reproductive behavior. Together these studies will assess the role of CCK in male copulatory behavior and the effects steroids have on modulating the distribution and release of CCK in male rats. These proposed studies are expected to shed significant light on the important questions of how steroidal information is encoded and integrated in the CNS to influence reproductive behavior.

本研究的主要目的是阐明 性腺类固醇环境与性腺的关系 类固醇敏感性胆囊收缩素的组织和功能 （CCK）回路是性二态性边缘系统的一部分 下丘脑系统。 这个相互关联的系统，包括 内侧杏仁核、终心房床核、 内侧视前核和腹内侧区域 下丘脑，与感觉和性的整合有关 类固醇信号参与中枢神经系统对生殖行为的控制。 神经活性肽的性别二态性分布 边缘-下丘脑系统中的 CCK 似乎是 类固醇作用的重要化学标记，尤其是 因为在这个系统中 CCK 的类固醇调节机制 男性的合成可能与女性不同。 最初，我们建议描述之间的相互作用 成年男性的性腺类固醇和 CCK 回路 确定维持所需的睾酮代谢 边缘系统-下丘脑 CCK 回路。 检查类固醇 对CCK释放的影响，将采用体外灌注。 在 为了获得类固醇作用的形态特征 CCK 细胞，类固醇放射自显影和 CCK- 的组合 免疫组织化学将用于确定 CCK 细胞是否 男性集中类固醇。 为了开始阐明 边缘-下丘脑内类固醇信息的整合 系统，逆行束追踪将与类固醇相结合 放射自显影和免疫组织化学。 CCK的作用 男性边缘-下丘脑系统将通过注射进行测试 CCK 进入该系统中的离散基因座。 最后，要了解 性腺类固醇在发育过程中的组织作用，一系列 的老鼠的围产期性类固醇环境将发生改变 产生在生殖方面性别逆转的成年人 行为。 在两个平行组的大鼠中，CCK-的分布 这些大鼠的边缘-下丘脑系统中的阳性细胞将 被确定并与CCK的影响相关联 生殖行为。 这些研究将共同​​评估其作用 CCK 在男性交配行为中的作用以及类固醇的影响 调节雄性大鼠 CCK 的分布和释放。 这些拟议的研究预计将提供重要的启示 类固醇信息如何编码的重要问题 并整合到中枢神经系统中以影响生殖行为。