Increased Serum Levels of C21 Steroids in Female Patients With Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is one of the most common neurological diseases. This neurodegenerative autoimmune disease manifests as inflammatory and demyelinating impairment of the central nervous system (CNS). Although some studies demonstrated associations between altered steroidogenesis and pathophysiology of MS as well as the importance of steroids in the pathophysiology of MS, the knowledge concerning the steroid metabolome in female patients is limited. Hence, 51 steroids and steroid polar conjugates were measured in the serum of 12 women with MS, untreated with steroids and 6 agecorresponding female controls with the use of gas chromatography -mass spectrometry (GC-MS). The data were processed using age adjusted ANCOVA, receiver operating characteristics (ROC) analysis and orthogonal projections to latent structures (OPLS). Our data show higher levels of circulating C21 steroids including steroid modulators of ionotropic type A γ-aminobutyric acid (GABA A) receptors and glutamate receptors. Furthermore, the levels of GABAergic androsterone and 5-androsten-3β,7α,17β-triol were also higher in the female MS patients. In conclusion, the data demonstrate higher levels of circulating C21 steroids and their polar conjugates and some bioactive C19 steroids in women with MS, which may influence neuronal activity and affect the balance between neuroprotection and excitotoxicity.

A method for determination of one hundred endogenous steroids in human serum by gas chromatography-tandem mass spectrometry.

“…Due to the high number of analytes and variety of steroids measured in human circulation, a comparison of all steroids with results from other methods was unachievable. Nevertheless, a number of our present results are comparable with those data from our previously published GC-MS method (Bicikova et al 2013, Hill et al 2010b, Hill et al 2011a, Hill et al 2011b, Hill et al 2010c, Kancheva et al 2011, Majewska et al 2014, Parizek et al 2016 as well as with the results of other authors (for review see Hill et al 2010b).…”

“…In addition, this method currently includes the largest spectrum of human circulating steroids and steroid polar conjugates, at least for the GC-MS/MS platform. As have been demonstrated in our previous papers, steroid profiling enables various pathologies to be rapidly diagnosed (Bicikova et al 2013, Hill et al 2010c, Kanceva et al 2015, Parizek et al 2016, Sosvorova et al 2015. The present GC-MS/MS method includes a wide range of analytes, which reflect activities of most steroidogenic enzymes.…”

“…Steroid profiling helps various pathologies to be rapidly diagnosed. Moreover, the results from analyses investigating steroidogenic pathways may be used as a tool for uncovering pathology causations and proposals of new therapeutic approaches (Bicikova et al 2013, Hill et al 2010c, Kanceva et al 2015, Parizek et al 2016, Sosvorova et al 2015, Sterzl et al 2017.…”

Analytical Methods for the Determination of Neuroactive Steroids

“…Due to the high reproducibility, sensitivity, and availability of mass spectrum databases, GC-MS and GC-MS/MS techniques have often been used in these studies [72]. The most common ionization technique applied in metabolic studies based on GC is electron impact ionization (EI) [81,88,89]. This hard ionization technique can help to achieve the reproducible fragmentation of molecules [18,81].…”

Roles of Progesterone, Testosterone and Their Nuclear Receptors in Central Nervous System Myelination and Remyelination

“…In fact, levels of important neurosteroids were found to be suppressed in the white matter of MS patients [88] and decreased concentrations of sex steroids were associated with higher serum levels of proinflammatory cytokines [89,90]. On the other hand, in female patients with MS, higher levels of circulating steroids have been measured, including pregnenolone, progesterone, allopregnanolone and their polar conjugates, which may influence neuronal activity and affect the balance between neuroprotection and excitotoxicity [91].…”