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Title: Physiological studies investigating the actions of novel reproductive hormones
Author: Narayanaswamy, Shakunthala
ISNI:       0000 0004 5917 7425
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Infertility is becoming increasingly more common, affecting 1 in 6 couples in the UK and an estimated 48.5 million couples worldwide. Although there are a number of hormonal treatments, there has been very little advance in new treatments in the last decade. However, assisted reproductive therapies including in vitro fertilisation (IVF) are being more commonly used and in fact 2% of babies were conceived in the UK through IVF in 2012, although the average pregnancy rate per cycle has remained stable at only 20% for several years. Therefore, there is a huge scope for developing new treatments to help with the rising problem of infertility. Kisspeptin is a hypothalamic hormone that was associated for the first time with reproduction in 2003 and is now emerging as a possible novel future therapeutic for reproductive and fertility disorders. Kisspeptin signalling is vital for normal reproductive function and critically regulates GnRH secretion in response to metabolic and environmental cues. Previous research studies have shown that kisspeptin can be administered safely to humans with no side effects and therefore, my research builds on this previous work. I have focused on investigating how best to optimise the use of kisspeptin for future therapy, by firstly examining which isoform of kisspeptin is more potent and how this compares to GnRH (a current treatment modality). Secondly, I investigated whether continuous subcutaneous administration of kisspeptin would be a viable treatment modality, as in the future kisspeptin could be administered in a subcutaneous pump device and managed at home by the patient. I also investigate how baseline oestradiol levels may influence the gonadotrophin response to kisspeptin. Lastly, I investigate how kisspeptin interacts with two other neuropeptides to affect gonadotrophin secretion, by coadministration of them in healthy males.
Supervisor: Dhillo, Waljit ; Jayasena, Channa ; Owen, Bryn Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral