Mechanism of Estrogen's Inhibitory Effects on Feeding

雌激素抑制摄食的机制

• 批准号: 6674692
• 负责人: LISA A ECKEL
• 金额: $ 7.3万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6674692
• 关键词: appetite; cholecystokinin; estrogen receptors; estrogens; estrus; female; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory rat; menstrual cycle; neurons; nutrient intake activity; overeating; receptor expression; satiations

DESCRIPTION (provided by applicant): The ovarian cycle has profound effects on food intake in a variety of species, including humans. This effect is very prominent in female rats which display a 20 - 40 percent decrease in food intake during the estrous (sexually receptive) phase of the cycle. This decline in food intake during estrus appears to be mediated, at least in part, by increased sensitivity to the satiety effects of cholecystokinin (CCK), a gut peptide that is released during meals and functions to decrease food intake by generating a satiety signal that is relayed to the brain via the vagus nerve. The importance of the rat's ovarian cycle in the control of food intake is revealed by ovariectomy, which increases food intake, decreases sensitivity to CCK, promotes body weight gain and, in the absence of estrogen replacement, induces obesity. Although the decline in estrogen activity appears to mediate the hyperphagia and associated body weight gain following ovariectomy, it is not known whether changes in endogenous estrogen activity mediate the decrease in food intake and increase in CCK satiation expressed during estrus in cycling rats. One goal of this proposal is to determine whether antagonism of central estrogen receptor activity will block the estrous-related decrease in food intake and increase in CCK satiation. To investigate this hypothesis, food intake and meal patterns will be monitored in cycling rats treated with an antiestrogen at various phases of the estrous cycle. A second goal is to use c-Fos immunocytochemistry, a marker of neuronal activity, to determine whether increased sensitivity to the satiety effects of CCK during estrus is mediated by increased responsivity of neurons that process satiety signals generated by consumption of a meal and by injection of CCK. A third goal of this proposal is to determine the brain areas where endogenous estrogen acts to decrease food intake and increase CCK satiation during estrus. In this experiment, in situ hybridization and immunocytochemistry techniques will be combined to determine whether those neurons that are activated by CCK express estrogen receptors. Together, these studies have the potential to broaden our understanding of the mechanism by which food intake is controlled across the estrous cycle of female rats. Because eating disorders are more prevalent in women than in men, this proposal targets an important research question with clear clinical relevance .

描述（由申请人提供）：卵巢周期对包括人类在内的多种物种的食物摄入有深远的影响。这种效果在雌性大鼠身上非常明显，在月经周期的发情期（性接受期），雌性大鼠的食物摄入量会减少20% - 40%。发情期食物摄取量的减少，至少部分是由对胆囊收缩素（CCK）饱腹感的敏感性增加所介导的，CCK是一种肠道肽，在进餐时释放，通过产生饱腹感信号，通过迷走神经传递给大脑，从而减少食物摄取量。卵巢切除术揭示了大鼠卵巢周期在控制食物摄入方面的重要性，它增加了食物摄入，降低了对CCK的敏感性，促进了体重增加，并且在没有雌激素替代的情况下，诱发了肥胖。虽然雌激素活性的下降似乎介导了卵巢切除术后的贪食和相关的体重增加，但内源性雌激素活性的变化是否介导了发情期大鼠食物摄入量的减少和CCK饱足表达的增加尚不清楚。本研究的目的之一是确定中枢雌激素受体活性的拮抗是否会阻断发情相关的食物摄入减少和CCK饱足增加。为了验证这一假设，研究人员将在发情周期的不同阶段对服用抗雌激素的大鼠进行食物摄入和饮食模式监测。第二个目标是使用c-Fos免疫细胞化学（神经元活动的标记物）来确定发情期间对CCK饱腹感的敏感性增加是否由处理进食和注射CCK产生的饱腹感信号的神经元的反应性增加介导。这个提议的第三个目标是确定内源性雌激素在发情期间减少食物摄入和增加CCK饱足的大脑区域。在本实验中，将结合原位杂交和免疫细胞化学技术来确定那些被CCK激活的神经元是否表达雌激素受体。总之，这些研究有可能扩大我们对雌性大鼠发情周期中食物摄入控制机制的理解。由于饮食失调在女性中比在男性中更为普遍，因此该提案针对的是一个具有明确临床相关性的重要研究问题。