Significance of determination of 11beta-hydroxysteroid dehydrogenase

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 26-40-Glucocorticoid Actions & Disease
Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-40
Marie Bicikova*, Lucie Sosvorova, Jana Kubatova, Ludmila Macova, Richard Hampl and Luboslav Starka
Institute of Endocrinology, Prague, Czech Republic
Two decades ago scientists were interested mainly in the activity of 11β-hydroxysteroid dehydrogenase (11β-HSD) type II and to its mineralocorticoid receptors protective activity. Hand in hand with the study of neuroactive steroids and neurosteroids (NAS) it was discovered how necessary is the knowledge of activities both 11β-HSD isoenzymes I and II in various disease. It was documented that 11β-HSD is responsible not only for oxido-reductive transformations of glucocorticoids but also for metabolism of dehydroepiandosterone  (DHEA) and its 7-hydroxylated metabolites known as potent NAS. Recent results indicate that abnormal levels of DHEA and its 7-hydroxylated metabolites may play a negative role in neurodegenerative diseases.

Our new study focused on a possible role of 11βHSD and above named NAS in cerebrospinal fluid of patients with hydrocephalus, enabling prediction and consequent targeted treatment of dementia, which, after initial relief, appears in most of the patients. We predict the crucial role of 11β-HSD in the pathogenesis of hydrocephalus.

Similar principle of disturbed levels of 7-hydroxylated DHEA metabolites (produced mainly in glial cells) could be caused by the disturbances in 11β-HSD activity in another very serious disease – multiple sclerosis.

   The above mentioned steroids act as regulators of local cortisol activity due to their competition in the cortisol-cortisone balance mediated by 11β-HSD. 7-Hydroxy-dehydroepiandrosterone is marketed as anti-obesity dietary supplement, though no clinical study has appeared until now. The aim of our other most recent project was to contribute to the discovery of new hormonal factors involved in the formation and development of obesity in children.

Currently, we are studying the role 11β-HSD in men with fertility disturbances where enzyme activity could be negatively affected by endocrine disruptors resulting in extensive glucocorticoid activity.  The consequence of it is the inhibition of gene expression of LH receptors in Leydig cells and the disorders in testosterone and sperm production. We hope that results of our studies summarized here could lead to a new therapeutic approaches of disorders outlined above.

The works are supported by the grants IGA NT/13369, NT/12349-4, NT 13542-3 from the Czech Ministry of Health.

 

Nothing to Disclose: MB, LS, JK, LM, RH, LS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The works are supported by the grants IGA NT/13369, NT/12349-4, NT 13542-3 from the Czech Ministry of Health.
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