Regulation of Leptin Expression and Function in the Anterior Pituitary

垂体前叶瘦素表达和功能的调节

• 批准号: 0240907
• 负责人: Gwen Childs
• 金额: $ 34.26万
• 依托单位: University of Arkansas Medical Sciences Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-15 至 2007-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0240907&HistoricalAwards=false
• 关键词: Regulation; Leptin; Expression; Function; Anterior

Leptin is a protein that is normally produced by fat cells to signal the body when there is sufficient fat storage. Leptin signals the brain to regulate food intake, limiting expansion of fat cells. However, sufficient levels of fat cells are important for animal or human reproduction. Thus, the secretion of leptin by fat cells becomes a signal that must rise to critical levels before an animal can go through puberty and reproduce normally. Both leptin and leptin receptors have been found on anterior pituitary cells, which suggest that leptin may also be produced by one cell type to regulate another. This study will focus on this new site for leptin production and regulation. We will test the hypothesis that pituitary gonadotropes can be stimulated to produce leptin by hormones that regulate appetite or reproduction. We will determine if growth hormone cells have leptin receptors and how these receptors are regulated. Since GH breaks down fat cells, these studies may show that that inhibiting GH may be a protective mechanism to allow sufficient fat storage for puberty and onset or maintenance of pregnancy. To that end, we will learn if leptin from gonadotropes inhibits growth hormone (GH) production by pituitary somatotropes. This proposed study uses cell physiology and cell chemistry approaches and experiments to determine how leptin, and its receptors, are regulated in enriched populations of somatotropes and gonadotropes. It will then co-culture these cells to learn if gonadotropes can indeed inhibit somatotropes by their production of leptin. This would be the first demonstration of a pituitary circuit, mediated by leptin, that links hormones that regulate food intake and storage with those that regulate reproductive functions. These studies will provide opportunities for training and development of student and teachers, including underrepresented minorities. Discoveries made under this NSF award will allow the PI to discuss new roles for leptin and provide workshops on obesity and proper nutrition for K-12 teachers and their students.

瘦素是一种蛋白质，通常由脂肪细胞产生，当有足够的脂肪储存时，向身体发出信号。瘦素向大脑发出信号，调节食物摄入量，限制脂肪细胞的扩张。然而，足够的脂肪细胞水平对于动物或人类的生殖是重要的。因此，脂肪细胞分泌的瘦素成为一种信号，必须上升到临界水平，动物才能度过青春期并正常繁殖。瘦素和瘦素受体均在垂体前叶细胞上被发现，这表明瘦素也可能由一种细胞类型产生，以调节另一种细胞类型。这项研究将集中在瘦素产生和调节的这个新的部位。我们将验证这样一个假设，即调节食欲或生殖的激素可以刺激脑下垂体促性腺激素产生瘦素。我们将确定生长激素细胞是否有瘦素受体，以及这些受体是如何调节的。由于生长激素分解脂肪细胞，这些研究可能表明，抑制生长激素可能是一种保护机制，为青春期和怀孕的开始或维持提供足够的脂肪储存。为此，我们将了解促性腺激素中的瘦素是否会抑制脑下垂体促生长激素(GH)的产生。这项拟议的研究使用细胞生理学和细胞化学的方法和实验来确定瘦素及其受体是如何在丰富的生长激素和促性腺激素群体中调节的。然后，它将与这些细胞共同培养，以了解促性腺激素是否真的能通过产生瘦素来抑制生长激素。这将是由瘦素介导的脑下垂体回路的首次展示，该回路将调节食物摄取和储存的激素与调节生殖功能的激素联系起来。这些研究将为学生和教师，包括代表人数不足的少数群体提供培训和发展的机会。在这个NSF奖项下的发现将使PI能够讨论瘦素的新角色，并为K-12教师和他们的学生提供关于肥胖和适当营养的研讨会。