Physiological roles of the peptide prokineticin 1

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.