Gender-specific role of GPR30 estrogen receptors in controlling gastrointestinal functions.

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Functional gastrointestinal disorders are frequent reasons for patients to seek medical help and are associated with impaired quality of life. Prevalences of dyspepsia and irritable bowel syndrome ranges from 10 to 15 %. Drug treatment options of these functional disorders are limited and mostly consist of different symptomatic therapeutic approaches. Interestingly functional gastrointestinal disorders are more frequent in females, at least females more frequently seek medical advice.The GPR30 receptor is a recently reported receptor which was shown to be a possible target for estrogens. Localisation and function of this receptor are unknown. The suggested project wants to investigate whether GPR30 receptors are localized in the gastrointestinal tract and if so, to identify the functional meaning of these receptors. Our translational approach comprises studies in human tissue and for more sophisticated characterisation we will employ mice. Employing PCR and immunohistochemistry we aim to localize GPR 30 in the gastrointestinal tract followed by in vitro pharmacological and electrophysiological experiments that will allow us to comment on the possible functional relevance of GPR30 in the control of gastrointestinal function. Building on these experiments we intend to perform experiments in in vivo models mimicking symptoms of irritable bowel syndrome in order to identify possible GPR30 actions on gastrointestinal motility, diarrhoea, visceral sensation and inflammation. An important overarching aim is to identify possible gender differences in GPR30 expression or function. In summary the project intends to explore the role of GPR30 in the control of gastrointestinal function and to characterize whether GPR30 is a suitable target for future treatment of functional gastrointestinal disorders.