CONTROL OF GNRH DURING LACTATION: ROLE OF NPY AND LEPTIN

哺乳期间 GNRH 的控制：NPY 和瘦素的作用

• 批准号: 2857396
• 负责人: REBECCA S BROGAN
• 金额: $ 3.67万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2857396
• 关键词: antisense nucleic acid; bioperiodicity; gonadotropin releasing factor; hormone regulation /control mechanism; hypothalamic pituitary axis; laboratory rat; lactation; leptin; neuroendocrine system; neuropeptide Y; pituitary gonadal axis

Although the inhibition of normal ovarian cyclicity and ovulation that accompanies lactation is thought to result from the suppression of GnRH secretion, little is known about the neuronal systems in the hypothalamus that mediate the suppression of GnRH neuronal function. During lactation, the hypothalamus must integrate the effects of neural input arising from the suckling stimulus and of metabolic signals arising from the energy drain of milk production, which result in increased food intake. Thus, important systems to study would be those that have dual roles in the regulation of both reproductive function and food intake. The proposed studies will investigate two such systems, neuropeptide Y (NPY) and leptin. Using the lactating rat as a model, I will test the hypothesis that the changes in NPY and leptin shown to occur during lactation contribute to the inhibition of GnRH secretion. Data will be collected on physiological and neuroanatomical indices, such as LH and leptin secretion, and NPY and leptin receptor mRNA distribution. The use of antisense technology to block NPY action and administration of leptin will be employed to determine the relative contributions of each in the inhibition of GnRH/LH secretion. These studies will provide the first detailed characterization of changes in leptin and the leptin receptor during lactation and will determine whether changes in NPY and leptin play a causal role in the suppression of reproductive function during lactation.

虽然抑制正常的卵巢循环和排卵 伴随泌乳被认为是由GNRH抑制而产生的 分泌，对神经元系统知之甚少 下丘脑介导GnRH神经元功能的抑制。 在泌乳过程中，下丘脑必须整合神经的作用 哺乳刺激和代谢信号产生的输入 由牛奶生产的能源流失引起的，这导致 增加食物摄入量。 因此，重要的研究系统将是 在生殖功能和 食物摄入量。拟议的研究将调查两个这样的系统， 神经肽Y（NPY）和瘦素。 使用泌乳大鼠作为模型， 我将检验以下假设，即NPY和瘦素的变化显示为 泌乳期间发生有助于抑制GnRH分泌。 数据将收集有关生理和神经解剖学指数的数据， 例如LH和瘦素分泌，NPY和瘦素受体mRNA 分配。 使用反义技术阻止NPY动作和 将使用瘦素的给药来确定相对 每个人在抑制GnRH/LH分泌方面的贡献。 这些 研究将提供第一个详细的变化表征 哺乳期瘦素和瘦素受体，将确定 NPY和瘦素的变化是否在抑制中起因果作用 泌乳过程中生殖功能。