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: 7337067
• 负责人: LISA A ECKEL
• 金额: $ 24.9万
• 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/7337067
• 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; Condition; 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; Personal Satisfaction; 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.

卵巢激素雌二醇对大多数（如果不是全部）神经系统有深远的影响。因此，在本发明中， 雌二醇影响多种生理功能，从而影响行为。在其各种行动中， 雌二醇对食物摄入具有强有力的抑制作用，在多种物种中均有表达，包括 人类近年来，雌二醇的这种作用与饮食失调的发生有关，例如 以及食欲增加和体重增加，这是经常观察到的雌二醇缺乏，绝经后 妇女了解雌二醇如何导致这些疾病的关键第一步是 确定它如何影响健康动物的食物摄入控制。现有证据表明， 雌二醇对食物摄入的抑制作用是通过其增加其他关键蛋白的强度的能力来介导的。 满足感信号系统中的元素。在这里，我们建议调查几个基本的 关于雌二醇和5-羟色胺（5-HT）的可能相互作用的问题，其中一种饱腹感信号，在 控制雌性大鼠的食物摄入。 分子技术将用于研究我们的中心假设，即5-HT的增加 神经传递介导雌激素在雌性大鼠中的厌食作用。在具体目标1和2中，我们 将建立大脑区域，这是必要的和足够的雌激素抑制食物摄入。 在具体目标3中，我们将确定是否增加突触后5-HT 2C受体的激活， 有助于雌激素抑制食物摄入。在具体目标4中，我们将确定雌二醇是否 作用于中脑中缝系统，增加特定脑内5-HT的释放和/或周转 控制食物摄入的区域。成功完成这些研究将扩大我们的 了解雌二醇的厌食作用的行为和神经生物学机制。 因为我们的研究重点是雌二醇和5-HT在控制食物中的相互作用， 在患有神经性厌食症的妇女中已经确定了维生素E摄入和维生素E能功能的异常， 这项工作的完成有可能揭示雌二醇是如何作为一个危险因素发挥作用的， 相关疾病。因此，该提案针对具有明确临床相关性的重要研究问题。