Dynorphin and Kappa-Opioid Receptor-Mediated Regulation of the Ovulatory Luteinizing Hormone Surge

强啡肽和卡帕阿片受体介导的排卵黄体生成激素激增的调节

• 批准号: 9807546
• 负责人: Robert Gallo
• 金额: $ 16万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-15 至 2002-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9807546&HistoricalAwards=false
• 关键词: Dynorphin; Kappa; Opioid; Receptor; Mediated

Robert Gallo IBN 9807546 A decrease in the inhibitory influence of endogenous opioid peptides on luteinizing hormone (LH) secretion is important in the regulation of the ovulatory LH surge. This suppression is postulated to be exerted by beta-endorphin originating in arcuate nucleus neurons and acting via mu- opioid receptors. The potential involvement of other opioid peptides and their receptors in "disinhibition" of the LH surge has not been explored. Recent work in Dr. Gallo's lab suggests that reduction in medial preoptic area (MPOA) kappa- opioid receptor-mediated inhibitory tone may be a critical event in the generation of the LH surge. This proposal has two specific aims designed to clarify the mechanisms underlying MPOA kappa-opioid receptor-mediated suppression of the LH surge. (1) Because dynorphin is the endogenous ligand for the kappa-opioid receptor, the first aim will be to determine which of the end products of prodynorphin processing are the active ligands in the MPOA mediating suppression of LH secretion. (2) The second aim will be to determine whether reduction in MPOA kappa-opioid receptor- mediated suppression of the LH surge is due to a decrease in the number of kappa-opioid receptors, the affinity of the kappa receptors for its endogenous ligand, and/or the synthesis of prodynorphin in the MPOA preceding the LH surge. These experiments will broaden our understanding of the role of the prodynorphin family of opioid peptides in reproductive neuroendocrine function by clarifying their role in the mechanisms regulating the ovulatory LH surge.

Robert Gallo IBN 9807546 内源性阿片肽对黄体生成素 (LH) 分泌的抑制影响的降低对于排卵 LH 激增的调节非常重要。 这种抑制被认为是由源自弓状核神经元并通过 mu-阿片受体作用的 β-内啡肽发挥的。 其他阿片肽及其受体在 LH 激增“去抑制”中的潜在参与尚未被探索。 Gallo 博士实验室最近的工作表明，内侧视前区 (MPOA) kappa-阿片受体介导的抑制性张力的减少可能是 LH 激增产生的关键事件。 该提案有两个具体目标，旨在阐明 MPOA kappa-阿片受体介导的 LH 激增抑制机制。 (1) 由于强啡肽是 κ-阿片受体的内源性配体，因此首要目标是确定强啡肽原加工的最终产物中哪些是 MPOA 介导 LH 分泌抑制的活性配体。 (2) 第二个目标是确定 MPOA kappa-阿片受体介导的 LH 激增抑制的减少是否是由于 kappa-阿片受体数量、kappa 受体与其内源配体的亲和力减少和/或 LH 激增之前 MPOA 中强啡肽合成的减少所致。 这些实验将通过阐明阿片肽强啡肽原家族在调节排卵 LH 激增的机制中的作用，拓宽我们对阿片肽强啡肽原家族在生殖神经内分泌功能中的作用的理解。