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Title: The role of augurin in the hypothalamo-pituitary-adrenal axis and the regulation of food intake
Author: Tadross, John Alphonse
ISNI:       0000 0004 2710 2242
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Novel secreted peptides represent an important field of research because delineation of their function affords new insights into the pathophysiological processes causing disease, and provides opportunities for the development of pharmacological therapies. Augurin is a recently identified secreted peptide of unknown function expressed in the central nervous system (CNS), pituitary, and several endocrine tissues. Because of its expression pattern I hypothesised that augurin may be involved in the neuroendocrine system. I therefore investigated the effects of central injection of augurin on the hypothalamo-pituitary axes and food intake in male Wistar rats. Intracerebroventricular (ICV) or intraparaventricular nucleus (iPVN) injection of augurin increased plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels compared with vehicle-injected controls. Augurin also increased the release of corticotrophin releasing hormone (CRH) from hypothalamic explants, and pre-treatment with a CRH receptor antagonist in vivo prevented the rise in ACTH and corticosterone caused by ICV augurin, suggesting activation the hypothalamo-pituitary-adrenal (HPA) axis via by the release of CRH from neurons in the PVN. In addition to stimulating the HPA axis, iPVN injection of augurin at the start of either the light or dark phase caused a robust increase in food intake. To assess whether augurin might have a physiological role in the regulation of the HPA axis or food intake, I investigated its endogenous distribution in the rat CNS using immunohistochemistry and in situ hybridisation histochemistry. Augurin positive neurons were present in several regions of the CNS including the hypothalamus and the dorsal vagal complex of the brainstem, a distribution consistent with a possible role in neuroendocrine function. Augurin is therefore anatomically positioned to play a role in the hypothalamic regulation of the HPA axis and food intake. While the data presented suggest a novel role for augurin, these are preliminary studies. Currently, little is known about the physiology of the augurin system. Further characterisation of the neuroanatomy, identification of receptors, and the development of receptor agonists and antagonists would provide further data on the physiological role of augurin, and on the potential therapeutic benefits of manipulating the augurin system.
Supervisor: Patterson, Michael ; Ghatei, Mohammad ; Bloom, Stephen Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral