The regulation of 11 beta-hydroxysteroid dehydrogenase type 1 by ageing and glucocorticoids in key tissues

Sherlock, Mark (2011). The regulation of 11 beta-hydroxysteroid dehydrogenase type 1 by ageing and glucocorticoids in key tissues. University of Birmingham. Ph.D.

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Abstract

In recent decades, the control of cortisol metabolism within tissues by the 11 beta-hydroxysteroid dehydrogenase (11 β-HSD) enzyme system has been studied in detail, however there is limited data regarding the effect of this enzyme system on skeletal muscle. The results of this thesis show that 11 β-HSD1 is biologically active in skeletal muscle.
11 β-HSD1 plays a key role in glucocorticoid (GC) mediated myopathy by increasing atrophy pathways, decreasing hypertrophy pathways and inhibiting myoblast proliferation. There are many similarities between glucocorticoid mediated myopathy and the muscle loss associated with ageing (sarcopaenia). We have shown that 11 β-HSD1 is increased with age in murine skeletal muscle and this may have a key role to play in the development of sarcopaenia. Further work is required in this area to examine the impact of modulation of 11 β-HSD1 on muscle with ageing.
We have shown that hypopituitary patients receiving hydrocortisone replacement therapy have significant alterations in cortisol metabolites and an increase in 11 β-HSD1. The alterations in cortisol metabolism are associated with an adverse body composition. New modified release hydrocortisone preparations, which replace cortisol in a more physiological manner, need to be assessed for their impact on cortisol metabolism.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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