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

Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

• Klíčová slova
• Alzheimer’s disease, GC-MS, differential diagnostics, multivariate statistics, steroidome, type 2 diabetes mellitus,
• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• androstendion MeSH
• diabetes mellitus 2. typu * diagnóza   epidemiologie   MeSH
• komorbidita MeSH
• lidé MeSH
• steroidy metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androstendion MeSH
• steroidy MeSH

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM- women (n = 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

• Klíčová slova
• gas chromatography-tandem mass spectrometry, gestational age, gestational diabetes mellitus, immunoprotective steroids, maternal blood, mixed cord blood, neuroactive steroids, steroidome,
• MeSH
• 20-hydroxysteroid dehydrogenasy metabolismus   MeSH
• chromatografie plynová MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• druhý trimestr těhotenství metabolismus   MeSH
• gestační diabetes metabolismus   MeSH
• lidé MeSH
• metabolomika metody   MeSH
• oxidoreduktasy metabolismus   MeSH
• steroid-17-alfa-hydroxylasa metabolismus   MeSH
• steroidy analýza   MeSH
• tandemová hmotnostní spektrometrie MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 20-hydroxysteroid dehydrogenasy MeSH
• 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase MeSH Prohlížeč
• 3-oxo-5 beta-steroid delta 4-dehydrogenase MeSH Prohlížeč
• CYP17A1 protein, human MeSH Prohlížeč
• CYP3A7 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• oxidoreduktasy MeSH
• steroid-17-alfa-hydroxylasa MeSH
• steroidy MeSH

Anorexia nervosa (AN) is associated with various alterations including the dysfunction of the HPA axis and consequently the hypercortisolemia and deficit in sex hormones but the comprehensive evaluation of changes in circulating steroids during the hospitalization of AN patients is lacking. We investigated the effect of realimentation of women with AN during hospitalization on 45 circulating steroids, the relationships between BMI, its change during hospitalization and physical activity, on one side and initial levels and their changes for two adipokines, circulating steroids, anorexia-specific (hunger, appetite and satiety), and anorexia non-specific symptoms (anxiety, depression fatigue, sleep, and body pain) on the other side. We included 33 women with anorexia who were hospitalized for 38(35, 44) days (median with quartiles). The increase of BMI from the initial value 15.2 (13.2, 16.6) kg/m2 was 1.69 (1.37, 2.66) kg/m2. The patients with more severe anorexia showed higher activity in 7β-, and 16α-hydroxylation of androgen precursors, which declined during hospitalization. Otherwise, the 7α-hydroxylation activity is higher in AN patients with less severe malnutrition and the ratio of 5-androstene-3β,7α,17β-triol to 5-androstene-3β,7β,17β-triol increased during the realimentation. Our data allow to speculate that the intensive 7β-, and 16α- and possibly also the 7α-hydroxylation of C19 Δ5 steroids participate in the pathophysiology of anorexia by additional catabolism of substrates available for synthesis of active androgens and estrogens. However, the question remains whether the synthetic analogues of 7α/β- and 16α-hydroxy-steroids prevent the catabolism of the sex steroid precursors, or further activate the "energy wasting" mitochondrial thermogenic metabolism.

• Klíčová slova
• Anorexia nervosa, Anxiety, Depression, Refeeding, Specific symptoms and physical activity, Steroid metabolome,
• MeSH
• dospělí MeSH
• hospitalizace MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• mentální anorexie metabolismus   psychologie   MeSH
• mladý dospělý MeSH
• steroidy krev   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• steroidy MeSH

Spa treatment can effectively reestablish mood balance in patients with psychiatric disorders. In light of the adrenal gland's role as a crossroad of psychosomatic medicine, this study evaluated changes in 88 circulating steroids and their relationships with a consolidation of somatic, psychosomatic and psychiatric components from a modified N-5 neurotic questionnaire in 46 postmenopausal 50+ women with anxiety-depressive complaints. The patients underwent a standardized one-month intervention therapy with physical activity and an optimized daily regimen in a spa in the Czech Republic. All participants were on medication with selective serotonin reuptake inhibitors. An increase of adrenal steroidogenesis after intervention indicated a reinstatement of the hypothalamic-pituitary-adrenal axis. The increases of many of these steroids were likely beneficial to patients, including immunoprotective adrenal androgens and their metabolites, neuroactive steroids that stimulate mental activity but protect from excitotoxicity, steroids that suppress pain perception and fear, steroids that consolidate insulin secretion, and steroids that improve xenobiotic clearance. The positive associations between the initial values of neurotic symptoms and their declines after the intervention, as well as between initial adrenal activity and the decline of neurotic symptoms, indicate that neurotic impairment may be alleviated by such therapy provided that the initial adrenal activity is not seriously disrupted.

• Klíčová slova
• adrenal, mood balance, postmenopausal females, spa treatment, steroid metabolome,
• MeSH
• afekt * MeSH
• cvičení * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadledviny metabolismus   MeSH
• postmenopauza * MeSH
• projektivní techniky MeSH
• psychoterapie * MeSH
• senioři MeSH
• steroidy biosyntéza   MeSH
• určení symptomu MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• steroidy MeSH

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.

• MeSH
• 17-alfa-hydroxypregnenolon krev   chemie   MeSH
• 17-alfa-hydroxyprogesteron krev   chemie   MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• dospělí MeSH
• gestační stáří MeSH
• hydrokortison krev   chemie   MeSH
• intrahepatální cholestáza diagnóza   metabolismus   patologie   MeSH
• jaterní testy MeSH
• komplikace těhotenství diagnóza   metabolismus   patologie   MeSH
• lidé MeSH
• nuclei raphe dorsalis MeSH
• plocha pod křivkou MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• radioimunoanalýza MeSH
• ROC křivka MeSH
• steroidy krev   chemie   metabolismus   MeSH
• těhotenství MeSH
• žlučové kyseliny a soli analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 17-alfa-hydroxypregnenolon MeSH
• 17-alfa-hydroxyprogesteron MeSH
• alanintransaminasa MeSH
• aspartátaminotransferasy MeSH
• hydrokortison MeSH
• steroidy MeSH
• žlučové kyseliny a soli MeSH

Alzheimer's disease (AD) represents more than half of total dementias. Various factors including altered steroid biosynthesis may participate in its pathophysiology. We investigated how the circulating steroids (measured by GC-MS and RIA) may be altered in the presence of AD. Sixteen women with AD and 22 age- and BMI-corresponding controls aged over 65 years were enrolled in the study. The steroid levels (47 steroids and steroid polar conjugates) and their ratios in AD female patients indicated increased CYP11A1 activity, weakened activity of the CYP17A1C17,20 lyase metabolic step and attenuated sulfotransferase SULT2A1 activity at higher activity of the CYP17A1 17-hydroxylase step. The patients showed diminished HSD3B2 activity for C21 steroids, abated conversion of 17-hydroxyprogesterone to cortisol, and significantly elevated cortisol. The women with AD had also attenuated steroid 7α-hydroxylation forming immunoprotective Δ(5)-C19 steroids, attenuated aromatase activity forming estradiol that induces autoimmunity and a shift from the 3β-hydroxy-5α/β-reduced C19 steroids to their neuroinhibitory and antiinflammatory GABAergic 3α-hydroxy- counterparts and showed higher levels of the 3α-hydroxy-5α/β-reduced C21 steroids and pregnenolone sulfate (improves cognitive abilities but may be both protective and excitotoxic). Our preliminary data indicated functioning of alternative "backdoor" pathway in women with AD showing higher levels of both 5α/β-reduced C21 steroids but reduced levels of both 5α/β-reduced C21 steroids, which implied that the alternative "backdoor" pathway might include both 5α- and 5β-reduced steroids. Our study suggested relationships between AD status in women based on the age of subjects and levels of 10 steroids measured by GC-MS.

• Klíčová slova
• Alzheimer’s disease, GC–MS, Multivariate statistics, RIA, Steroid metabolome, Women,
• MeSH
• Alzheimerova nemoc krev   metabolismus   MeSH
• hormony krev   MeSH
• lidé MeSH
• oxidoreduktasy metabolismus   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• progesteronreduktasa metabolismus   MeSH
• senioři MeSH
• sulfotransferasy metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• zona reticularis metabolismus   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3 beta-hydroxysteroid dehydrogenase type II MeSH Prohlížeč
• 3-oxo-5 beta-steroid delta 4-dehydrogenase MeSH Prohlížeč
• alcohol sulfotransferase MeSH Prohlížeč
• hormony MeSH
• oxidoreduktasy MeSH
• progesteronreduktasa MeSH
• sulfotransferasy MeSH
• systém (enzymů) cytochromů P-450 MeSH

In this review we focused on steroid metabolomics in human fetuses and newborns and its role in the physiology and pathophysiology of human pregnancy and subsequent stages of human life, and on the physiological relevance of steroids influencing the nervous systems with regards to their concentrations in the fetus. Steroid profiling provides valuable data for the diagnostics of diseases related to altered steroidogenesis in the fetal and maternal compartments and placenta. We outlined a potential use of steroid metabolomics for the prediction of reproductive disorders, misbalance of hypothalamic-pituitary-adrenal axis, and impaired insulin sensitivity in subsequent stages of human life. A possible role of steroids exhibiting a non-genomic effect in the development of gestational diabetes and in the neuroprotection via negative modulation of AMPA/kainate receptors was also indicated. Increasing progesterone synthesis and catabolism, declining production of tocolytic 5β-pregnane steroids, and rising activities of steroid sulfotransferases with the approaching term may be of importance in sustaining pregnancy. An increasing trend was demonstrated with advancing gestation toward the production of ketones (and 3β-hydroxyl groups in the case of 3α-hydroxy-steroids) was demonstrated in the fetus on the expense of 3α-hydroxy-, 17β-hydroxy-, and 20α-hydroxy-groups weakening in the sequence C17, C3, and C20. There was higher production of active progestogen but lower production of active estrogen and GABAergic steroids with the approaching term. Rising activities of placental CYP19A1 and oxidative isoforms of HSD17B, and of fetal CYP3A7 with advancing gestation may protect the fetus from hyperestrogenization. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

• Klíčová slova
• Cord blood, GC–MS, Labor, Metabolome, Steroids,
• MeSH
• estrogeny fyziologie   MeSH
• hormony kůry nadledvin fyziologie   MeSH
• lidé MeSH
• mozek metabolismus   MeSH
• plod metabolismus   MeSH
• pohlavní steroidní hormony fyziologie   MeSH
• progestiny fyziologie   MeSH
• těhotenství MeSH
• vývoj plodu MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• estrogeny MeSH
• hormony kůry nadledvin MeSH
• pohlavní steroidní hormony MeSH
• progestiny MeSH