ECE2014 Poster Presentations Steroid metabolism and action (12 abstracts)
Profiling of neuroactive steroids, their precursors and metabolites in patients suffering from multiple sclerosis
Radmila Kancheva 1 , Martin Hill 1 , Lyudmila Kancheva 1 , Marta Velikova 1 , Miluse Pavelcova 2 , Luboslav Starka 1 & Eva Havrdova 2
1Institute of Endocrinology, Prague, Czech Republic; 2Department of Neurology, First Faculty of Medicine, Center of Demyellinating Diseases, Charles University, Prague, Czech Republic.
Some steroids modulate the permeability of ionotropic receptors on cell membranes and therefore may activate or inhibit neuronal activity depending on the steroid structure. These neuroactive steroids (NAS) exert neuroprotective effects like the neuronal remyelination.
Multiple sclerosis (MS) is the most common cause of neurological disability in young adults. Therefore, the authors have followed the neuroprotective, GABAergic, glycinergic, glutamatergic acetylcholinergic and purinergic NAS, their precursors and metabolites and their conjugates (64 steroids)in the Δ4 and Δ5 steroidogenic pathways, estrogens, 5α/β-reduced pregnanes and androstanes (both 17-oxo and 17β-hydroxy), 7α/β- and 16α-hydroxyderivatives of the Δ5 steroids, and 20α-hydroxyderivatives of the Δ4 and Δ5 steroids, and 5α/β-reduced pregnanes in the circulation and cerebrospinal fluid of 13 female patients – 36 years old median age and 8 sex age matched healthy controls (both in the follicular menstrual phase) with the use of gas chromatography – mass spectrometry. The steroid conjugates were hydrolyzed and the released steroids were detected like the case of the unconjugated ones. The primary finding was the increased levels of C21 steroids in body fluids, which points to increased activity of adrenal cortex as mechanism enabling a consequent synthesis of neuroprotective steroids in various human peripheral tissues. The neuroprotective effects of individual steroids and a possible utilization of the results for the diagnosis and treatment of MS were discussed.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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