Nantia Othonos

My research focuses on the interaction between exogenous glucocorticoids and enzymes that are able to metabolize them and modify their action. In particular I am looking at the role of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and the 5a-reductases .  

2-3% of the population of the UK are prescribed steroid treatment to treat a wide variety of conditions. Whilst steroid treatment is very effective, it is associated with a significant number of side effects that can include weight gain, the development of diabetes, high blood pressure, fat in the liver and thinning of the muscles.  

11β-HSD1 is highly expressed in metabolic tissues and we hypothesized that AZD4017, an inhibitor of 11β-HSD1, will reduce the adverse metabolic consequences of exogenous glucocorticoids, by decreasing the amount of active cortisol in the bloodstream. On the other hand, 5a-reductases increase the amount of active cortisol and thus 5a-reductase inhibitors such as Finasteride + Dutasteride could potentially augment the metabolic side-effects of exogenous glucocorticoids. Finasteride + Dutasteride are commonly prescribed medications for people who suffer from prostate problems.  My research aims to investigate the metabolic effects of an exogenous glucocorticoid, Prednisolone, when taken in combination with AZD4017 or a 5a-reductase inhibitor.