LEPTIN ENHANCES PITUITARY GONADAL AXIS AFTER FOOD RESTRICTION IN MALE MONKEYS

瘦素在雄性猴子的食物限制后增强垂体性腺轴

• 批准号: 6277396
• 负责人: HAROLD G SPIES
• 金额: $ 7.42万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277396
• 关键词: Mammalia; Primates; biological products; clinical research; endocrine gland /system; male; nervous system; nutrition; nutrition related tag; reproductive system; women's health

Leptin is a hormonal product of adipocytes that has a role in the regulation of body weight and metabolism. In rodents, this fat-regulating substance acts as a metabolic signal to the reproductive axis and can reverse the inhibitory effects of food restriction on pubertal age and gonadotropin secretion. Numerous clinical studies in humans have reported correlations between leptin levels and metabolic (and weight) changes, but the role of leptin, if any, on the primate reproductive axis is unknown. Using a food restriction protocol that our colleague Dr. J. Cameron had shown to inhibit pulsatile luteinizing hormone (LH) in rhesus monkeys, we designed a study to determine if leptin could reverse this food-restricted LH inhibition. We fasted (water only) male monkeys (4-6 kg), Macaca mulatta, for 44 hours (h), during which time the animals received either leptin (134 g/kg BW/h, iv) or saline. Nightly patterns of LH were bioassayed using the mouse interstitial cell testosterone assay in blood samples that were collected every 20 minutes for two 12 h periods (before and 32-44 h after onset of the fast) and hourly for the first 18 h of the fast. In 4 of 4 monkeys treated with saline, there was complete suppression of LH pulses during fasting. Conversely, 3 of 4 leptin-treated monkeys showed distinct pulses of LH during the last 8 h of the fast. Moreover, mean LH levels during the same period were higher in the leptin-treated animals than in the vehicle-treated controls. Patterns of blood testosterone (T) in the individual males of the two groups showed similar trends to those of LH, although the 8-h mean levels of T between the leptin- and vehicle-groups were not different (P > 0.05). Our collaborators at the University of Washington are identifying possible neural targets for leptin's action by locating cells that contain leptin receptor mRNA. The results suggest that in primates, as in rodents, leptin is a metabolic signal to the reproductive axis and that neuropeptide Y and/or proopiomelanocortin containing cells may be mediators of leptin's action in the brain. Future efforts will focus on completion and publication of the findings, since the studies may provide a foundation for understanding relationships between eating disorders and certain reproductive problems.

瘦素是脂肪细胞的一种荷尔蒙产物，在 调节体重和新陈代谢。在啮齿动物中，这是 脂肪调节物质作为代谢信号传递给 并能逆转食物对生殖轴的抑制作用 对青春期年龄和促性腺激素分泌的限制。数不胜数 人类临床研究报告了瘦素与瘦素之间的相关性 水平和代谢(和体重)的变化，但瘦素的作用，如果 灵长类生殖轴上的任何一个都是未知的。使用一种食物 我们的同事J.卡梅伦博士向我们展示的限制协议 抑制恒河猴搏动性黄体生成素(LH) 设计了一项研究，以确定瘦素是否可以逆转这一趋势 食物受限的促黄体生成素抑制。我们禁食(仅限饮水)雄性猴子 (4-6公斤)，猕猴，44小时(小时)，在此期间 动物接受瘦素(134克/公斤体重/小时，静脉注射)或生理盐水。每晚 用小鼠间质细胞生物测定促黄体生成素的模式 每隔20天采集一次的血液样本中的睾酮检测 两个12小时的时间段(发病前和发病后32-44小时) 快速)，并且在禁食的前18小时每小时。在4只猴子中有4只 用生理盐水治疗后，黄体生成素脉冲完全被抑制 在禁食期间。相反，4只接受瘦素治疗的猴子中有3只表现出 在禁食的最后8小时内，有明显的黄体生成素脉冲。此外，刻薄 在同一时期，接受瘦素治疗的患者的促黄体生成素水平更高 动物比在车辆处理过的对照中。血型 两组男性个体的睾酮(T)水平显示 与黄体生成素类似的趋势，尽管8小时平均T水平 瘦素组与赋形剂组之间差异无统计学意义(P&gt；0.05)。 我们在华盛顿大学的合作者正在识别 瘦素可能的神经靶点通过定位 含有瘦素受体mRNA。结果表明，在灵长类动物中， 与啮齿动物一样，瘦素是生殖轴的代谢信号。 神经肽Y和/或含前阿片黑素皮质素的细胞 可能是瘦素在大脑中作用的中介物。未来的努力将 将重点放在完成和发布调查结果上，因为研究 可以为理解 饮食失调和某些生殖问题。