Leptin and Reproduction in Free-Ranging Bats

长期以来，人们一直认为哺乳动物体内存在一种调节体重的循环因子。这种激素，现在被称为瘦素，于1994年被发现，并被发现从脂肪组织中分泌。瘦素向大脑发出信号，降低食欲，提高代谢率。最近，包括人类在内的几种哺乳动物在怀孕期间血液中的瘦素水平明显升高。这一点，以及其他证据，导致了一种假设，即瘦素可能在维持妊娠和准备哺乳方面发挥着以前未被认识但却很重要的作用。这项申请中提出的工作旨在研究这一假说，首先通过确定怀孕期间哪些组织分泌瘦素，然后通过确定哪些因素控制其分泌，并最终确定瘦素在怀孕动物身上发挥什么功能。通过测量培养皿中动物组织产生的少量瘦素，这些目标将得到促进。威德迈尔博士提出，在怀孕期间，胎盘成为循环中瘦素的重要来源，雌激素和皮质醇等生殖激素会刺激胎盘中瘦素的产生。威德迈尔博士还提出，怀孕期间大脑对瘦素的敏感度降低，从而导致怀孕期间食欲增加。这些问题将在自由放养的蝙蝠中进行测试。更好地了解生殖的荷尔蒙相关性不仅将提高我们治疗人类生殖障碍的能力，而且将提高我们成功维持生态重要动物物种种群的能力。最后，更好地了解瘦素的作用和对其分泌的控制将提高我们对人类和动物群体中体重病理的理解。

9875871WidmaierThe existence of a circulating factor that regulates body weight in mammals has long been postulated. This hormone, now known as leptin, was identified in 1994, and found to be secreted from adipose (fat) tissue. Leptin signals the brain to reduce appetite and increase metabolic rate. Recently, it has become apparent that leptin levels in the blood are elevated during pregnancy in several mammalian species, including human beings. This, and other evidence, has led to the hypothesis that leptin may play previously unrecognized but important roles in the maintenance of pregnancy and the preparation for lactation. The work proposed in this application is designed to investigate this hypothesis, first by determining what tissues secrete leptin during pregnancy, then by determining what factors control its secretion, and ultimately determining what functions leptin performs in the pregnant animal. These goals will be facilitated by the ability to measure small amounts of leptin production from animal tissues in the culture dish. Dr. Widmaier proposes that the placenta becomes a significant source of circulating leptin during pregnancy and that reproductive hormones like estrogen and cortisol stimulate leptin production in placenta. Dr. Widmaier also proposes that the brain becomes less sensitive to leptin during pregnancy, permitting an increased appetite during pregnancy. These questions will be examined in free-ranging bats. A better appreciation of the hormonal correlates of reproduction will not only improve our ability to treat reproductive disorders in people, but will increase our ability to successfully maintain populations of ecologically important animal species. Finally, a better appreciation of the actions of leptin and the control of its secretion will improve our understanding of body weight pathologies in human and animal populations.