Estradiol, MCH and Food Intake

雌二醇、MCH 和食物摄入量

• 批准号: 7545160
• 负责人: Jessica C Santollo
• 金额: $ 3.1万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-13 至 2011-06-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545160
• 关键词: Acute; Affect; Animals; Anorexia Nervosa; Appetitive Behavior; Automobile Driving; Binding; Binding Sites; Biological; Biological Factors; Brain; Brain region; Cell Nucleus; Cholecystokinin; Data; Desire for food; Development; Disease; Eating; Eating Disorders; Elements; Endocrine system; Estradiol; Estrogen Nuclear Receptor; Estrogen Receptors; Estrous Cycle; Feeding behaviors; Female; Gene Expression; Glucagon; Goals; Human; Hypothalamic structure; Immunohistochemistry; Infusion procedures; Knowledge; Label; Laboratories; Lateral; Learning; Ligands; Localized; Mediating; Modeling; Neurons; Neuropeptides; Neurotransmitters; Numbers; Obesity; Ovarian; Ovarian hormone; Peptides; Personal Satisfaction; Physiological; Play; Prevalence; Proteins; Rattus; Reporting; Research; Risk Factors; Rodent; Role; Scientist; Series; Serotonin; Sex Characteristics; Signal Transduction; Site; Staging; System; Techniques; Testing; Ventricular; Woman; Work; behavior test; feeding; hindbrain; hormone deficiency; immunocytochemistry; increased appetite; melanin-concentrating hormone; melanin-concentrating hormone receptor; men; neuromechanism; protein expression; relating to nervous system; transcription factor; zona incerta

DESCRIPTION (provided by applicant): Despite the fact that eating disorders are more prevalent in women than in men, the mechanism driving this sex difference is poorly understood. While environmental and cultural factors likely contribute to the greater prevalence of eating disorders in women, it is becoming increasing clear that biological factors may also play a key role. In recent years, the ovarian hormone estradiol, which exerts a potent anorexigenic effect in variety of species including humans, has emerged as a putative, biological risk factor for eating disorders in general, and anorexia nervosa in particular. A crucial first step in understanding how estradiol may contribute to eating disorders is to determine how it affects the normal controls of food intake in healthy animals. Available evidence suggests that the anorexigenic effect of estradiol is mediated indirectly through interactions with other key elements of the neural and endocrine systems controlling ingestive behavior. While it is well established that estradiol increases the female rat's sensitivity to anorexigenic (appetite suppressing) peptides and neurotransmitter systems, my preliminary data suggest that estradiol is also capable of decreasing the female rat's sensitivity to an orexigenic (appetite stimulating) neuropeptide, melanin-concentrating hormone (MCH). In the present application, I propose to examine the neural mechanisms underlying estradioPs ability to decrease MCH-induced feeding. My working hypothesis is that estradiol acts via nuclear estrogen receptors (ERs) to decrease MCH signaling and, as a consequence, decreases food intake. Using single-label immunohistochemistry, I will determine whether estradiol decreases MCH or MCH receptor (MCHR1) protein expression in brain regions implicated in the control of food intake. I will also combine site-specific infusions of estraidol with ventricular infusions of MCH in order to identify brain region(s) in which estradiol acts to decrease MCH-induced feeding. Finally, I will investigate whether ERs are expressed within the same neurons that express MCH and MCHR1. This series of studies has the potential to increase our understanding of the mechanism underlying estradiol's anorexigenic effect and this knowledge may ultimately reveal how estradiol functions as a risk factor for certain eating-related disorders. In completing this research, I will learn new techniques and further my professional development, allowing me to reach my ultimate goal of becoming an independent scientist.

描述（由申请人提供）：尽管饮食失调在女性中比男性更普遍，但对这种性别差异的机制知之甚少。虽然环境和文化因素可能导致女性饮食失调的患病率更高，但越来越明显的是，生物因素也可能发挥关键作用。近年来，卵巢激素雌二醇在包括人类在内的各种物种中发挥了强有力的促食欲作用，已成为一般饮食失调，特别是神经性厌食症的推定生物风险因素。了解雌二醇如何导致进食障碍的关键第一步是确定它如何影响健康动物对食物摄入的正常控制。现有证据表明，雌二醇的促雌激素作用是通过与控制摄食行为的神经和内分泌系统的其他关键要素相互作用间接介导的。 虽然它是公认的雌二醇增加雌性大鼠的食欲（食欲抑制）肽和神经递质系统的敏感性，我的初步数据表明，雌二醇也能够降低雌性大鼠的食欲（食欲刺激）神经肽，黑色素浓缩激素（MCH）的敏感性。在本申请中，我建议研究雌激素降低MCH诱导的摄食能力的神经机制。我的工作假设是雌二醇通过核雌激素受体（ER）减少MCH信号传导，从而减少食物摄入。使用单标记免疫组织化学，我将确定雌二醇是否降低MCH或MCH受体（MCHR1）蛋白表达在大脑区域涉及控制食物摄入。我还将结合联合收割机雌激素的特定部位输注和MCH的脑室输注，以确定雌二醇作用于减少MCH诱导的摄食的脑区。最后，我将研究ER是否在表达MCH和MCHR1的相同神经元中表达。这一系列的研究有可能增加我们对雌二醇的致癌作用机制的理解，这些知识可能最终揭示雌二醇如何作为某些饮食相关疾病的风险因素。在完成这项研究的过程中，我将学习新技术，进一步发展我的专业，使我能够达到成为一名独立科学家的最终目标。