Physiological roles of the peptide Prokineticin 1
File(s)
Author(s)
Abbara, Ali
Type
Thesis
Abstract
Prokineticin-1 (PK-1) and prokineticin-2 (PK-2) are two closely related cysteine-rich peptides which both bind to the prokineticin-1 and prokineticin-2 receptors (PKR-1 and PKR-2). The prokineticins were originally named due to their ability to stimulate gastrointestinal motility. Since that time, these peptides have been found to play a role in other biological processes including reproduction and nociception. Prokineticin-2 is known to be expressed in regions of the central nervous system involved in food intake. Consistent with this, work from our own department has shown that administration of prokineticin-2 to rodents reduces food intake both in lean and obese rodents.
Prokineticin-2 is predominantly expressed within the central nervous system, whereas prokineticin-1 is heavily expressed in the gut. My pilot data showed that prokineticin 1 reduces food intake in rodents. I therefore hypothesised that prokineticin 1 may be a novel gut hormone. In this thesis, I investigate the role of prokineticin-1 on appetite in rodents and also compare the effects of prokineticin-1 with prokineticin-2. I also measured the changes in plasma levels of prokineticin in humans during feeding to establish the potential physiological relevance of prokineticin-1 as an anorectic gut hormone.
Prokineticin-1 is also a potent angiogenic mitogen on endocrine vascular epithelium and hence it is also known as ‘Endocrine Gland-Vascular Endothelial Factor’. Placental angiogenesis plays an important role in placental function and risk of pregnancy complications such as miscarriage. I therefore hypothesised that prokineticin-1 is a biomarker of pregnancy complications in humans. In this thesis, I have measured circulating levels of prokineticin-1 found in pregnancy and correlated these with the occurrence of pregnancy complications. I have also compared the utility of prokineticin 1 with other potential novel markers of pregnancy complications. Together this body of work investigates the potential physiological roles of prokineticin-1.
Prokineticin-2 is predominantly expressed within the central nervous system, whereas prokineticin-1 is heavily expressed in the gut. My pilot data showed that prokineticin 1 reduces food intake in rodents. I therefore hypothesised that prokineticin 1 may be a novel gut hormone. In this thesis, I investigate the role of prokineticin-1 on appetite in rodents and also compare the effects of prokineticin-1 with prokineticin-2. I also measured the changes in plasma levels of prokineticin in humans during feeding to establish the potential physiological relevance of prokineticin-1 as an anorectic gut hormone.
Prokineticin-1 is also a potent angiogenic mitogen on endocrine vascular epithelium and hence it is also known as ‘Endocrine Gland-Vascular Endothelial Factor’. Placental angiogenesis plays an important role in placental function and risk of pregnancy complications such as miscarriage. I therefore hypothesised that prokineticin-1 is a biomarker of pregnancy complications in humans. In this thesis, I have measured circulating levels of prokineticin-1 found in pregnancy and correlated these with the occurrence of pregnancy complications. I have also compared the utility of prokineticin 1 with other potential novel markers of pregnancy complications. Together this body of work investigates the potential physiological roles of prokineticin-1.
Version
Open Access
Date Issued
2014-07
Date Awarded
2014-10
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Dhillo, Waljit
Jayasena, Channa
Gardiner, James
Sponsor
Wellcome Trust (London, England)
Grant Number
P34470
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)