Endocrine Abstracts

Multiple sclerosis (MS) is a common inflammatory autoimmune and demyelinating disease of the central nervous system (CNS) that compromises health and leads to disability. Sex differences in the prevalence and progression of MS suggest the involvement of sex steroids in the pathophysiology of MS. In late pregnancy, at the highest levels of progesterone and estradiol, the number of relapses decreases and increases again after delivery due to changes in steroid levels. In addition, dehydroepiandrosterone (DHEA) and its derivatives may also influence the development of MS. Therefore, the correlations between circulating steroid levels in MS patients were evaluated with respect to the pathophysiology of MS. The levels of endogenous steroids (n=85) (quantified using the GC-MS/MS platform) in serum samples from 23 fertile-aged follicular menstruating women with multiple sclerosis and 7 premenopausal women (n=7) before treatment were simultaneously compared with age-matched controls (n=16) using a multivariate regression with dimensionality reduction (orthogonal projection to latent structure, OPLS) including the age of the volunteers. The presence of MS was negatively correlated with serum endogenous steroid levels, with steroid levels explaining 29% of the presence of MS. The analytes included sulphates of Δ⁵ pregnanes (glutamate and negative GABA_A receptor modulators) and androstanes, their free analogues, neuroprotective and immunoprotective 7α-hydroxy, 7-oxo-, 7β-hydroxy and 16α-hydroxy-metabolites of Δ⁵ androstanes, progestogens (bioactive progesterone, 20α-dihydroprogesterone, 17-hydroxyprogesterone, its free and conjugated 20α-dihydrometabolite, 16α-hydroxyprogesterone) inactive Δ⁴ androgen androstenedione, bioactive Δ⁴ androgens testosterone and 5α-dihydrotestosterone including its conjugated form, estrogens estrone sulfate and bioactive estradiol, a variety of 5α/β reduced free and conjugated 20-oxo and 20α-dihydropregnanes (including GABAergic positive modulators with hydroxyl in the 3α-position, glutamate receptor modulators). Furthermore, the analytes measured included 5α/β-reduced free and conjugated androgens also including a number of neuroactive steroids and finally the active corticosteroids cortisol and corticosterone as well as the inactive cortisol metabolite cortisone and finally 11β-hydroxy-androstanes. It was found that 28 steroids were significantly negatively correlated with MS. These steroids included a number of bioactive substances including five neuroprotective and immunoprotective 7α-hydroxy, 7-oxo-, 7β-hydroxy-Δ⁵ androstanes, a number of GABAergic positive modulators with a hydroxyl at the 3α-position, and two 11β-hydroxy androstanes. Thus, it is likely that lower serum levels of a number of bioactive steroids in MS patients could be related to the pathophysiology of this disease. Grant NU20-04-00450 from the Ministry of Health of the Czech Republic supported the study.