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The role of kisspeptin in reproduction

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Title: The role of kisspeptin in reproduction
Authors: Comninos, Alexander
Item Type: Thesis or dissertation
Abstract: Kisspeptin is a recently identified hypothalamic neuropeptide hormone which is a critical regulator of mammalian reproductive physiology. In addition, kisspeptin administration stimulates gonadotrophin release in all species tested. Kisspeptin may therefore serve as a potential therapy for reproductive pathologies. The role of kisspeptin has been studied extensively within the hypothalamus but little is known about its extra-hypothalamic effects. Using manganese-enhanced MRI to detect neuronal activity, I demonstrate marked decreases in neuronal activity in the amygdala of adult mice after kisspeptin administration. This data reveals a novel effect of kisspeptin with pharmacological implications. The human kisspeptin peptides kisspeptin-10, -13, -14, and -54 are named according to their constituent amino acids. Kisspeptin-10 is the smallest and most easily synthesised peptide from a pharmacological point of view. By investigating the effects of the kisspeptin-10 peptide in healthy men and women, I uncover a sexual dimorphism in gonadotrophin response to kisspeptin-10 as well as a greater potency of kisspeptin-54 over kisspeptin-10 in humans. Having established the effects of acute kisspeptin administration in healthy women, I investigated the effects of chronic administration of kisspeptin on reproductive function. Using biochemical and radiological parameters of menstrual cyclicity, I demonstrate that 7 days of kisspeptin administration advances the menstrual cycle in healthy women. In summary, in this thesis I have identified a novel effect of kisspeptin in rodents involving the amygdala. My clinical studies have identified for the first time the acute and chronic effects of kisspeptin administration in humans. Combined, these data have important implications for the development of kisspeptin as a potential therapy for reproductive pathologies.
Content Version: Open Access
Issue Date: Aug-2014
Date Awarded: Dec-2014
URI: http://hdl.handle.net/10044/1/33252
DOI: https://doi.org/10.25560/33252
Supervisor: Dhillo, Waljit
Jayasena, Channa
Sponsor/Funder: Wellcome Trust (London, England)
Funder's Grant Number: WMDI P40218
Department: Department of Medicine
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses

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