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Title: Regulation of P-glycoprotein and glucocorticoid receptor expression in the rat intestine
Author: Moodie, Fiona M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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We studied the expression of genes regulating steroid sensitivity in the healthy Wistar rat and found genes were differentially expressed along the length of the colon. Notably, P-gp expression was increased in proximal compared to distal colon. A reverse gradient was noted for GR. Systemic dexamethasone treatment as well as endogenous corticosterone were shown to regulate these genes, and thereby these data support a role for steroids regulating tissue sensitivity to steroids. To further clarify the role of bacteria and disease on expression of P-gp and GR, HLA-B27 transgenic and non-transgenic rats were studied. Colonic inflammation in HLA-B27 transgenic rats decreased P-gp and GR. Bacteria were also shown to regulate expression of these genes in a site-specific manner along the colon. These data emphasise the complex gene-bacterial interactions within the colon in health and disease. Dexamethasone administered to rats with/out inflammation differentially regulated GR expression in a site-specific manner along the colon. Steroid treatment did not alter P-gp expression in the inflamed colons. These data show the complexity of the intestinal regulation of these genes in the inflamed and non-inflamed colon; corticosteroid treatment may have selected efficacy in different regions of the colon. Collectively these data suggest a role for dexamethasone treatment as well as bacteria in the regulation of genes determining steroid sensitivity in the healthy and diseased rodent intestinal epithelium. The complex interaction between P-gp and GR expression in response to bacteria has implications for potential mechanisms by which inflammation is induced in the colon.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available