Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.600361
Title: Glucocorticoids, 11β-hydroxysteroid dehydrogenase type 1 and the aged phenotype
Author: Hassan-Smith, Zaki K.
ISNI:       0000 0004 5351 2288
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2014
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Abstract:
Cushing’s syndrome is characterised by changes in body composition and cardiovascular disease risk profiles that have similarities to the aged phenotype. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive glucocorticoids(GCs) to their active form (cortisone to cortisol in humans). There is growing evidence that 11β-HSD1 expression/activity increases with age in key target tissues including adipose tissue, bone, and skin. This thesis encompasses a series of novel studies investigating the role of GCs and their pre-receptor metabolism in determining the ageing phenotype, with a central focus on skeletal muscle. We show that although cure of Cushing’s disease results in rapid improvements in clinical parameters, excess mortality may persist. We show in-vitro evidence of regulation of proteolytic genes by 11β-HSD1 and that 11β-HSD1KO mice are protected from muscle weakness due to GCs and ageing. We recruited healthy subjects (n=135, 20-80 years) for in-depth phenotyping, along with muscle biopsies (analysed by gene expression array) and urine steroid metabolite analysis. Skeletal muscle 11β-HSD1 expression increased with age in women and this change may be driven by the menopause. The therapeutic potential of selective inhibitors of 11β-HSD1 in ameliorating the adverse metabolic and body composition profile associated with ageing and the menopause remains to be determined.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.600361  DOI: Not available
Keywords: R Medicine (General)
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