Hormone-neurotransmitter interactions in the control of food intake.

激素-神经递质相互作用在控制食物摄入中的作用。

• 批准号: 7545448
• 负责人: LISA A ECKEL
• 金额: $ 24.87万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545448
• 关键词: Accounting; Acute; Affect; Agonist; Animals; Anorexia Nervosa; Appetite Depressants; Automobile Driving; Behavior; Behavioral; Biological Assay; Brain; Brain region; Bulimia; Cell Nucleus; Cholecystokinin; Complex; Data; Desire for food; Development; Disease; Eating; Eating Disorders; Elements; Epidemiologic Studies; Estradiol; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptors; Estrus; Event; Female; Fenfluramine; Genes; Glucagon; Goals; Hormones; Human; Hyperphagia; Hypothalamic structure; ICI 182780; Injection of therapeutic agent; Laboratories; Link; Location; Mediating; Microdialysis; Microinjections; Midbrain structure; Middle Hypothalamus; Modeling; Molecular; Molecular Genetics; Nervous system structure; Neurons; Neurosciences; Neurotransmitters; Ovarian; Ovarian hormone; Peptides; Peripheral; Physiological; Play; Postmenopause; Preoptic Areas; Prevalence; Rattus; Research; Research Personnel; Risk Factors; Rodent; Role; Satiation; Serotonin; Serotonin Receptor 5-HT2C; Sex Characteristics; Signal Transduction; Site; System; Techniques; Testing; Tissues; Weight Gain; Woman; Work; base; clinically relevant; dorsal raphe nucleus; estrogenic activity; extracellular; feeding; in vivo; inhibitor/antagonist; malignant breast neoplasm; men; neurobiological mechanism; neurotransmission; paraventricular nucleus; postsynaptic; presynaptic; receptor; relating to nervous system; reuptake; serotonin receptor; steroid hormone; transcription factor

The ovarian hormone estradiol has profound effects on most, if not all, of the nervous system. As a result, estradiol influences a variety of physiological functions and,therefore, behavior. Among its varied actions, estradiol exerts a potent inhibitory effect on food intake that is expressed in a variety of species, including humans. In recent years, this action of estradiol has been linked to the development of eating disorders, as well as the increase in appetite and weight gain that is often observed in estradiol-deficient, postmenopausal women. A crucial first step in understanding how estradiol may contribute to either of these conditions is to determine how it affects the controls of food intake in healthy animals. Available evidence suggests that the inhibitory effect of estradiol on food intake is mediated by its ability to increase the strength of other key elements within the satiety-signaling system. Here, we propose to investigate several fundamental questions regarding the possible interaction of estradiol and serotonin (5-HT), one such satiety signal, in the control of food intake in the female rat.A combination of behavioral, pharmacological, antomical, and molecular techniques will be used to investigate our central hypothesis, which is that an increase in 5-HT neurotransmission mediates the anorectic effect of estradiol in the female rat. In Specific Aims 1 and 2, we will establish brain regions that are both necessary and sufficient for the estrogenic inhibition of food intake. In Specific Aim 3, we will determine whether increased activation of postsynaptic 5-HT2C receptors contributes to the estrogenic inhibition of food intake. In Specific Aim 4, we will determine whether estradiol acts with the midbrain raphe system to increase the release and/or turnover of 5-HT within specific brain regions implicated in the control of food intake. Successful completion of these studies will broaden our understanding of the behavioral and neurobiological mechanisms underlying the anorectic effect of estradiol. Because our proposed studies focus on an interactive effect of estradiol and 5-HT in the control of food intake, and abnormalities in serotonergic function have been identified in women with anorexia nervosa, completion of this work has the potential to reveal how estradiol may function as a risk factor for eating- related disorders. Thus, this proposal targets an important research question with clear clinical relevance.

卵巢激素雌二醇对神经系统的大部分(如果不是全部)都有深远的影响。结果, 雌二醇会影响多种生理功能，从而影响行为。在它的各种行动中， 雌二醇对食物摄取有很强的抑制作用，这种抑制作用在多种物种中都有表达，包括 人类。近年来，雌激素的这种作用被认为与饮食失调的发展有关，如 以及绝经后雌激素缺乏患者经常出现的食欲增加和体重增加 女人。要了解雌二醇对上述两种情况的作用，关键的第一步是 确定它如何影响健康动物的食物摄入量控制。现有证据表明， 雌二醇对食物摄取的抑制作用是通过增强其他关键点的力量来实现的。 饱腹感信号系统中的元素。在这里，我们建议调查几个基本问题 关于雌激素和5-羟色胺(5-羟色胺)可能相互作用的问题，5-羟色胺是一种这样的饱腹感信号，在 控制雌性大鼠的摄食量。行为学、药理学、安非他命和 分子技术将被用来研究我们的中心假设，即5-羟色胺的增加 神经传递介导雌二醇对雌性大鼠的厌食作用。在具体目标1和2中，我们 将建立对雌激素抑制食物摄取既必要又充分的大脑区域。 在特定的目标3中，我们将确定突触后5-HT2C受体的激活增加 有助于雌激素抑制食物的摄取。在特定的目标4中，我们将确定雌二醇是否 与中脑中缝系统共同作用，增加特定脑内5-羟色胺的释放和/或周转 涉及控制食物摄入量的地区。成功完成这些研究将扩大我们的 了解雌二醇厌食作用的行为和神经生物学机制。 因为我们建议的研究集中在雌二醇和5-羟色胺在控制食物中的交互作用上 摄入量和5-羟色胺能功能异常已经在患有神经性厌食症的女性中被发现， 这项工作的完成有可能揭示雌激素是如何作为进食的风险因素发挥作用的。 相关的障碍。因此，这项建议针对的是一个重要的研究问题，具有明确的临床相关性。