Kisspeptin antagonists: unraveling the role of kisspeptin in reproductive physiology

Robert P Millar, Antonia K Roseweir, Javier A Tello, Richard A Anderson, Jyothis T George, Kevin Morgan, Adam J Pawson

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)81-9
Number of pages9
JournalBrain Research
Volume1364
DOIs
Publication statusPublished - Dec 2010

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