POTENTIATION OF CCK-8 ON FOOD INTAKE BY ESTRADIOL

雌二醇对 CCK-8 食物摄入的增强作用

• 批准号: 3246995
• 负责人: PETER C BUTERA
• 金额: $ 7.57万
• 依托单位: NIAGARA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3246995
• 关键词: appetite regulatory center; brain mapping; cholecystokinin; estradiol; hormone regulation /control mechanism; hypothalamus; laboratory rat; neuroendocrine system; neuropeptide receptor; nutrient intake activity; nutrition related tag; ovariectomy; paraventricular nucleus; preoptic areas

Gonadal steroids are among the numerous factors influencing food intake and body weight in rats. Hormonal effects on these processes are particularly striking in females, which show large increases in food intake and body weight after ovariectomy. These changes can be reversed by peripheral treatment with estradiol or by direct placement of estradiol (E2) in the hypothalamic paraventricular nucleus (PVN). Although it is acknowledged that the effects of E2 on feeding require actions of the hormone within the brain, the neural mechanism by which E2 suppresses food intake remains to be specified. Peripheral injections of the hormone cholecystokinin (CCK) reduce food intake in a number of species, and CCK is now viewed as an important physiological signal for satiety. Manipulation of ovarian hormones has been shown to alter CCK activity in several hypothalamic nuclei, including the PVN, suggesting that the effects of E2 on feeding may be mediated by the modulation of CCK systems within the brain. Along these lines, it has recently been shown that peripheral treatment with E2 potentiates the effects of intraperitoneal (ip) injections of CCK on food intake in female rats. The proposed experiments will attempt to confirm and extend this phenomenon by identifying the brain site at which E2 acts to augment the satiety effect of CCK, and by examining the role played by central CCK receptors in this steroid-peptide interaction. It is hypothesized that E2 enhances CCK activity in the PVN , which in turn potentiates CCK's effects on food intake and mediates the suppressive effects of E2 on eating. The first experiment will evaluate this hypothesis by placing central implants of dilute E2 in the PVN, ventromedial nucleus of the hypothalamus (VMN) and preoptic area (POA)of female rats. It is also hypothesized that the potentiation of the satiety effect of CCK by E2 requires the stimulation of brain receptors for CCK in the PVN. The second experiment will examine the effects of PVN infusions of 2 different CCK receptor antagonists on the suppression of food intake produced by E2 alone, CCK alone and the combined treatment of E2 and CCK. Information obtained from these experiments will contribute to our understanding of brain mechanisms involved in feeding behavior and the ways in which steroid hormones affect brain function.

性腺类固醇是影响食物摄入的众多因素之一 和大鼠的体重。 激素对这些过程的影响是 特别是在雌性中， 卵巢切除术后的摄入量和体重。 这些变化是可以逆转的 通过雌二醇的外周治疗或通过直接放置 雌二醇（E2）在下丘脑室旁核（PVN）。 尽管人们承认E2对摄食的影响需要 大脑中激素的作用，E2的神经机制， 抑制食物摄入仍有待说明。 外周注射 激素胆囊收缩素（CCK）减少许多人食物摄入， CCK现在被认为是一种重要的生理信号， 饱腹感 卵巢激素的调控已被证明会改变CCK 活动在几个下丘脑核团，包括PVN，表明 E2对摄食的影响可能是通过调节 大脑中的CCK系统。 沿着这些路线，最近 表明E2的外周治疗增强了 腹腔注射CCK对雌性大鼠摄食量的影响。的 拟议中的实验将试图证实和扩展这一现象 通过确定E2作用于增强饱腹感的大脑部位， CCK的作用，并通过检查中央CCK受体所发挥的作用， 类固醇和肽的相互作用 据推测，E2增强了 PVN中的CCK活性，这反过来又增强了CCK对食物的影响 摄入和介导E2对进食的抑制作用。 第一 本实验将通过将中央植入物 稀释PVN、下丘脑腹内侧核（VMN）和 雌性大鼠的视前区（POA）。 还假设， E2增强CCK的饱腹感效应需要刺激 室旁核中CCK的脑受体 第二个实验将 检查PVN输注2种不同CCK受体的效果 拮抗剂对E2单独产生的摄食抑制，CCK E2和CCK联合治疗。 获得的信息 这些实验将有助于我们理解大脑 摄食行为的机制以及类固醇激素 激素影响大脑功能。