Investigation of the novel hormone kisspeptin in disorders of reproduction
Author(s)
Nijher, Gurjinder Monica Kaur
Type
Thesis
Abstract
The novel hormone kisspeptin has been identified to play a pivotal role in the regulation of
the hypothalamo-pituitary-gonadal axis. Previous studies from our laboratory have
demonstrated that a bolus administration of kisspeptin-54 can acutely stimulate
gonadotrophin release in healthy men and women. However, no previous studies have
examined the effects of kisspeptin-54 to women with infertility. In this study I have examined
the effects of acute and chronic administration of kisspeptin-54 on women with infertility due
to hypothalamic amenorrhoea. This study has identified that acute administration of
kisspeptin to women with hypothalamic amenorrhoea results in stimulation of reproductive
hormones, but chronic administration for two weeks of twice daily injections of kisspeptin-54
at a dose of 6.4 nmol/kg, results in tachyphylaxis. I have conducted further studies to
examine the time course of desensitisation of the kisspeptin receptor. I have also determined
that a dosing regime of twice weekly administration of kisspeptin-54 results in sustained
stimulation of gonadotrophin release. I have performed the first study of kisspeptin-10
administration to men and women. These results demonstrate that kisspeptin-10 stimulates
gonadotrophin release in men as well as women during the preovulatory phase of the
menstrual cycle; but fails to stimulate gonadotrophin release in women during the follicular
phase. This reveals a sexual dimorphism in response to the kisspeptin-10. These findings
have important ramifications for the potential use of kisspeptin-54 and kisspeptin-10 as a
therapeutic agent in disorders of reproduction.
the hypothalamo-pituitary-gonadal axis. Previous studies from our laboratory have
demonstrated that a bolus administration of kisspeptin-54 can acutely stimulate
gonadotrophin release in healthy men and women. However, no previous studies have
examined the effects of kisspeptin-54 to women with infertility. In this study I have examined
the effects of acute and chronic administration of kisspeptin-54 on women with infertility due
to hypothalamic amenorrhoea. This study has identified that acute administration of
kisspeptin to women with hypothalamic amenorrhoea results in stimulation of reproductive
hormones, but chronic administration for two weeks of twice daily injections of kisspeptin-54
at a dose of 6.4 nmol/kg, results in tachyphylaxis. I have conducted further studies to
examine the time course of desensitisation of the kisspeptin receptor. I have also determined
that a dosing regime of twice weekly administration of kisspeptin-54 results in sustained
stimulation of gonadotrophin release. I have performed the first study of kisspeptin-10
administration to men and women. These results demonstrate that kisspeptin-10 stimulates
gonadotrophin release in men as well as women during the preovulatory phase of the
menstrual cycle; but fails to stimulate gonadotrophin release in women during the follicular
phase. This reveals a sexual dimorphism in response to the kisspeptin-10. These findings
have important ramifications for the potential use of kisspeptin-54 and kisspeptin-10 as a
therapeutic agent in disorders of reproduction.
Date Issued
2012
Date Awarded
2012-11
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Bloom, Steve
Dhillo, Waljit
Publisher Department
Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)