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Title: Prostaglandin signalling in the human endometrium
Author: Milling Smith, Oliver Patrick
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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This thesis is based on the hypothesis that menstrual dysfunction, including heavy menstrual blood loss (MBL) is due to (a) up-regulated expression/synthesis of cycloxygenase enzymes and prostaglandin receptors, and (b) initiation of enhanced intracellular signalling pathways in response to prostaglandins. This thesis describes the use of an endometrial epithelial cell line to explore the molecular signalling pathways involved with the activation of a prostaglandin receptor – the prostacyclin receptor. A rapid activation of ERK1/2 signalling is demonstrated with alterations in expression of angiogenic factors via crosstalk with the epidermal growth factor receptor. By using endometrium collected from women with the complaint of heavy menstrual bleeding, the pattern of expression of the various components of the COX-prostaglandin signalling pathways present in the endometrium of women with normal and heavy MBL is elucidated. There is a significant elevation in expression of COX-1 and COX-2 mRNA in endometrium obtained from women with heavy MBL compared with endometrium obtained from women with normal MBL. Significant alterations in expression of downstream prostanoid synthase and prostanoid receptor mRNAs were also detected. Furthermore, enhanced prostaglandin stimulated production of cyclic AMP observed in endometrium of women with heavy MBL compared with normal MBL. By identifying the prostanoid receptors/signalling pathways that are responsible for disturbed endometrial function, this thesis aims to establish information that may result in the development of novel therapeutic targets for menstrual pathology.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available