Multiple sclerosis (MS) is a long-term disease that causes inflammation and damage to the nervous system. This study evaluated steroidomic alterations related to MS in 57 female MS patients during the follicular phase and 17 during the luteal phase, as well as in age- and phase-matched controls. The data showed that (1) unconjugated and conjugated steroids were strongly linked between the blood and CSF. (2) MS patients have lower levels of unconjugated steroids compared to controls. However, unchanged levels of conjugated steroids suggest a possible increase in steroid sulfotransferase functioning. (3) MS patients show altered levels of steroids linked to 11β-hydroxylase (CYP11B1) function. While direct enzyme activity was not measured, disrupted cortisol biosynthesis-potentially linked to reduced functioning of both CYP11B1 and 17α-hydroxylase/17,20-lyase-is associated with more severe cases of MS. (4) Reduced levels of 5α/β-steroids and protective GABAergic 3α-hydroxy-5α/β-steroids in MS patients might be linked to the pathophysiology of MS. (5) A potential increase in AKR1C3 function in MS could contribute to inflammation, as this enzyme catalyzes the synthesis of both steroids and prostaglandins. However, direct measurements of enzyme activity are needed to confirm this hypothesis. (6) Lower pregnenolone levels in MS patients might weaken neuroprotection, while higher pregnenolone sulfate levels could support cognitive function. (7) Lower levels of protective pregnenolone, DHEA, and androstenediol were associated with worse MS, suggesting these steroids may help shield against the disease.

• Klíčová slova
• GC-MS/MS, cerebrospinal fluid, multiple sclerosis, multivariate statistics, steroidomics,
• MeSH
• dospělí MeSH
• folikulární fáze mozkomíšní mok   MeSH
• lidé středního věku MeSH
• lidé MeSH
• luteální fáze mozkomíšní mok   MeSH
• mladý dospělý MeSH
• roztroušená skleróza * mozkomíšní mok   krev   MeSH
• steroidy * mozkomíšní mok   krev   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• steroidy * MeSH

BACKGROUND: Aging is associated with the development of various disorders, including postural imbalance, which increases the risk of falls and related health complications. This study examines changes in static postural balance after a 4-week intervention involving appropriate exercise and an optimized daily regimen. Additionally, it explores the relationship between these changes and the steroidome. METHODS: The study was conducted on a clinically homogeneous group of 41 females around their sixth decade, diagnosed with anxiety-depressive syndrome and treated with selective serotonin reuptake inhibitors (SSRIs). Postural balance was assessed using the dual-scales method (DLLL-DSM), which estimates postural imbalance by evaluating differences in the lower limb load in the standing position. Correlations between initial DLLL-DSM values, age, BMI, and the baseline levels of nine serum steroids, as well as post-intervention changes in five steroids, were analyzed using multivariate regression (OPLS model). RESULTS: A significant reduction in lower limb load differences (-ΔDLLL-DSM), indicating improved postural balance, was observed. The -ΔDLLL-DSM strongly correlated with initial DLLL-DSM values, age, BMI, initial levels of nine serum steroids, and post-intervention changes in five steroids (R = 0.892, p < 0.001). Furthermore, initial DLLL-DSM values negatively correlated with adrenal androgen androstenediol sulfate and various sulfated 5α/β-reduced androgen metabolites (R = 0.323, p < 0.05), suggesting that the activity of steroid sulfotransferase (SULT2A1) and C17-hydroxylase-C17,20-lyase (CYP17A1) at the lyase step is negatively associated with postural imbalance in elderly females. CONCLUSIONS: The findings suggest that even severe postural imbalance can be effectively and relatively rapidly improved through an appropriate exercise-based intervention and an optimized daily regimen, provided that initial adrenal activity is not significantly impaired. Additionally, the identified associations between steroid levels and postural balance provide new insights into the hormonal mechanisms regulating balance control in older individuals.

• Klíčová slova
• aging, exercise intervention, gas chromatography-tandem mass spectrometry, multivariate statistics, static postural balance, steroidome,
• Publikační typ
• časopisecké články MeSH

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. The manifestation of MS is related to steroid changes during the menstrual cycle and pregnancy. As data focusing on the effect of anti-MS drug treatment on steroidome are scarce, we evaluated steroidomic changes (79 steroids) in 61 female MS patients of reproductive age 39 (29, 47) years (median with quartiles) after treatment with anti-MS drugs on the GC-MS/MS platform and immunoassays (cortisol and estradiol). The changes were assessed using steroid levels and steroid molar ratios (SMRs) that may reflect the activities of steroidogenic enzymes (SMRs). A repeated measures ANOVA, followed by multiple comparisons and OPLS models, were used for statistical analyses. The anti-MS treatment decreased steroid levels in the follicular phase. Anti-CD20 monoclonal antibodies (mAb), such as ofatumumab and ocrelizumab; inhibitors of the sphingosine-1-phosphate receptor (S1PRI); and IFNβ-1a decreased circulating 17-hydroxy-pregnanes and shifted the CYP17A1 functioning from the hydroxylase- toward the lyase step. Decreased conjugated/unconjugated steroid ratios were found after treatment with anti-MS drugs, especially for glatiramer acetate and anti-CD20 mAb. In the luteal phase, IFN-β1a treatment increased steroidogenesis; both IFN-β1a and ocrelizumab increased AKR1D1, and S1PRI increased SRD5A functioning. Anti-CD20 mAb reduced the functioning of enzymes catalyzing the synthesis of immunomodulatory 7α/β and 16α-hydroxy-androgens, which may affect the severity of MS. The above findings may be important concerning the alterations in bioactive steroids, such as cortisol; active androgens and estrogens; and neuroactive, neuroprotective, and immunomodulatory steroids in terms of optimization of anti-MS treatment.

• Klíčová slova
• GC-MS/MS, anti-MS drugs, multiple sclerosis, multivariate statistics, steroidomics,
• MeSH
• dospělí MeSH
• glatiramer acetát terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• menstruační cyklus účinky léků   MeSH
• roztroušená skleróza * farmakoterapie   metabolismus   krev   MeSH
• steroidy * metabolismus   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glatiramer acetát MeSH
• steroidy * MeSH

The diagnostic prevalence of autism spectrum disorders (ASD) shows boys to be more affected than girls. Due to this reason, there is a lack of research including and observing ASD girls. Present study was aimed to detect hormones of steroidogenesis pathway in prepubertal girls (n = 16) diagnosed with ASD and sex and age matched neurotypical controls (CTRL, n = 16). Collected plasma served for detection of conjugated and unconjugated steroids using gas chromatography tandem-mass spectrometry. We observed higher levels of steroids modulating ionotropic receptors, especially, GABAergic steroids and pregnenolone sulfate in ASD group. Concentration of many steroids throughout the pathway tend to be higher in ASD girls compared to CTRL. Pregnenolone and its isomers together with polar progestins and androstanes, i.e. sulfated steroids, were found to be higher in ASD group in comparison with CTRL group. Based on steroid product to precursor ratios, ASD group showed higher levels of sulfated/conjugated steroids suggesting higher sulfotransferase or lower steroid sulfatase activity and we also obtained data indicating lower activity of steroid 11β-hydroxylase compared to CTRL group despite higher corticosterone level observed in ASD. These findings need to be generalized in future studies to examine both genders and other age groups.

• MeSH
• dítě MeSH
• lidé MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• poruchy autistického spektra * metabolismus   MeSH
• předškolní dítě MeSH
• pregnenolon * metabolismus   krev   MeSH
• steroidy metabolismus   krev   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• pregnenolon * MeSH
• pregnenolone sulfate MeSH Prohlížeč
• steroidy MeSH

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ5 androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts.

• Klíčová slova
• GC-MS/MS, differential diagnostics, multiple sclerosis, multivariate statistics, steroidomics,
• MeSH
• dospělí MeSH
• hydrokortison metabolismus   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• roztroušená skleróza * metabolismus   krev   MeSH
• steroidy metabolismus   MeSH
• studie případů a kontrol MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hydrokortison MeSH
• steroidy MeSH

Schizophrenia is associated with numerous abnormalities, including imbalances in all hormonal axes, among which steroids play a major role. Steroidomic studies therefore represent a promising tool for early diagnosis and appropriate treatment of schizophrenia. A total of 51 adult male schizophrenics aged 27 (22, 34) years (shown as median with quartiles) and 16 healthy controls (HCs) aged 28 (25, 32) years were enrolled into this study. Our results showed the effective differentiation of men with schizophrenia from controls based on steroidomic profiles. We also found an altered metabolic pathway from pregnenolone and its sulfate (PREG/S) to cortisol in schizophrenics with several metabolic bottlenecks such as lower PREG levels due to increased PREG sulfation and/or suppressed PREGS desulfation and attenuated conversion of 17-hydroxy-PREG to 17-hydroxy-progesterone, as well as the results suggestive of suppressed CYP11B1 activity. In contrast, steroid molar ratios suggested two counterregulatory steps involving increased conversion of PREG/S to 17-hydroxy-PREG/S and decreased conversion of cortisol to cortisone, which may maintain unchanged basal cortisol levels but may not ensure a sufficient cortisol response to stress. Our data also indicated a trend to higher 7α-, 7β-, and 16α-hydroxylation that may counteract the autoimmune complications and proinflammatory processes accompanying schizophrenia. Finally, a possible suppression of HSD17B3 activity was suggested, resulting in decreased circulating testosterone levels with increased androstenedione levels.

• Klíčová slova
• GC-MS/MS, differential diagnostics, multivariate statistics, schizophrenia, steroidomics,
• MeSH
• dospělí MeSH
• hydrokortison metabolismus   krev   MeSH
• lidé MeSH
• mladý dospělý MeSH
• pregnenolon metabolismus   krev   MeSH
• schizofrenie * metabolismus   MeSH
• steroidy metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hydrokortison MeSH
• pregnenolon MeSH
• steroidy MeSH

The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/β-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.

• Klíčová slova
• 7α/β-hydroxy-androgens, DHEA, androstenediol, behavioral immune system, cortisol, disgust, estrogens, pregnancy, steroids, testosterone,
• MeSH
• dospělí MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladý dospělý MeSH
• odpor * MeSH
• prospektivní studie MeSH
• první trimestr těhotenství MeSH
• steroidy krev   MeSH
• těhotenství MeSH
• třetí trimestr těhotenství krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• steroidy MeSH

Steroid hormones have diverse roles in pregnancy; some help stabilise pregnancy and influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies. To date, only a few studies have performed a very limited steroid analysis in multiple pregnancies. Our teams investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group, and a control singleton pregnancies group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35 + 3 to 39 + 3 weeks, while it was 38 + 1 to 41 + 1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies. Results demonstrate differences in the steroidome between singleton and twin pregnancies. These were based on the presence of two placentae and two foetal adrenal glands, both with separate enzymatic activity. Since every newborn was delivered by caesarean section, analysis was not negatively influenced by changes in the steroid metabolome associated with the spontaneous onset of labour.

• Klíčová slova
• foetomaternal steroidome, multiple pregnancy, neuroactive steroids, pregnancy complications,
• MeSH
• císařský řez MeSH
• kojenec MeSH
• lidé MeSH
• metabolom MeSH
• novorozenec MeSH
• retrospektivní studie MeSH
• steroidy MeSH
• těhotenství s dvojčaty * MeSH
• těhotenství MeSH
• výsledek těhotenství * MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• steroidy MeSH

UNLABELLED: Background: Only few studies have monitored the potential of physical activity training and physical therapy to modulate the reaction of the endocrine system. In this study, the effect of neuroproprioceptive facilitation and inhibition physical therapy on clinical outcomes and neuroactive steroids production in people with multiple sclerosis was evaluated. Moreover, we were interested in the factors that influence the treatment effect. METHODS: In total, 44 patients with multiple sclerosis were randomly divided into two groups. Each group underwent a different kind of two months ambulatory therapy (Motor program activating therapy and Vojta's reflex locomotion). During the following two months, participants were asked to continue the autotherapy. Primary (serum level of cortisol, cortisone, 7α-OH-DHEA, 7β-OH-DHEA, 7-oxo-DHEA, DHEA) and secondary (balance, cognition and patient-reported outcomes) outcomes were examined three times (pre, post, and washout assessments). RESULTS: In both groups, there is a decreasing trend of 7-oxo-DHEA concentration in post-assessment and 7β-OH-DHEA in washout versus pre-assessment. A higher impact on neuroactive steroids is visible after Vojta's reflex locomotion. As for clinical outcomes, the Paced Auditory Serial Addition Test and Multiple Sclerosis Impact Scale significantly improved between post-assessment and washout assessment. The improvement was similar for both treatments. CONCLUSIONS: Neuroproprioceptive facilitation and inhibition improved the clinical outcomes and led to non-significant changes in neuroactive steroids. Trial registration (NCT04379193).

• Klíčová slova
• cortisol, dehydroepiandrosterone, multiple sclerosis, neuroactive steroids, neuroproprioceptive facilitation and inhibition, physical therapy,
• Publikační typ
• časopisecké články MeSH

The etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent with the results reported in older children, in whom the adrenal zona reticularis significantly influences the steroid levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex hormones on one hand but increased anti-glucocorticoid effect of 7α-hydroxy-DHEA via competition with cortisone for HSD11B1 on the other. The multivariate model found significant correlations between behavioral indices and circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. The aforementioned data indicate a direction of the future research with a focus on the expression and functioning of genes associated with important steroidogenic enzymes in ASD patients from early childhood to adrenarche.

• MeSH
• biologické markery MeSH
• dítě MeSH
• lidé MeSH
• poruchy autistického spektra * MeSH
• předškolní dítě MeSH
• steroidy MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• steroidy MeSH