Medical Research Council Human Reproductive Sciences Unit, Edinburgh, UK.
Brain Res. 2010 Dec 10;1364:81-9. doi: 10.1016/j.brainres.2010.09.044. Epub 2010 Sep 18.
Kisspeptin has recently been identified as a key neuroendocrine gatekeeper of reproduction and is essential for the initiation of human puberty and maintenance of adult reproduction. Kisspeptin neurons appear to be integrative sensors, as they respond to changes in numerous internal and external factors including nutrient and fat status, stress and sex steroids, thus providing a link between these factors and reproduction. We have pioneered the development of kisspeptin antagonists as powerful tools for interrogating the role of kisspeptin in reproductive physiology and pathology, and as potential treatments for hormone-dependent disease. This article summarizes their development and key findings to date. These demonstrate an essential role for kisspeptin in GnRH neuron firing, GnRH pulsatile secretion, negative feedback by gonadal steroids, the onset of puberty, and the ovulatory LH surge. These studies establish that kisspeptin antagonists are powerful investigative tools and set the scene for more extensive physiological and pathophysiological studies as well as therapeutic intervention.
kisspeptin 最近被确定为生殖的关键神经内分泌守门员，对于人类青春期的开始和成人生殖的维持是必不可少的。 kisspeptin 神经元似乎是整合传感器，因为它们对许多内部和外部因素的变化做出反应，包括营养和脂肪状态、应激和性激素，从而在这些因素和生殖之间提供了联系。我们率先开发了 kisspeptin 拮抗剂，作为研究 kisspeptin 在生殖生理学和病理学中的作用的有力工具，以及作为治疗激素依赖性疾病的潜在方法。本文总结了它们的发展和迄今为止的关键发现。这些发现表明 kisspeptin 在 GnRH 神经元放电、 GnRH 脉冲式分泌、性腺类固醇的负反馈、青春期的开始和排卵 LH 激增中起着重要作用。这些研究确立了 kisspeptin 拮抗剂是强大的研究工具，并为更广泛的生理和病理生理学研究以及治疗干预奠定了基础。
