Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis
Abstract
1. Introduction
1.1. Origin and Role of Steroids in the Brain
1.2. Multiple Sclerosis and Steroids
1.2.1. Δ5 Steroids
1.2.2. Corticoids
1.2.3. GABAergic Steroids
2. Results
2.1. Correlations Between Steroids in Serum and Cerebrospinal Fluid
2.2. Alterations in Steroid Levels
2.2.1. Δ5 and Δ4 Steroids
2.2.2. 11β-Hydroxy-Androstanes (C19 Δ4 and 5α/β Steroids)
2.2.3. GABAergic Steroids
2.2.4. 17-oxo- and 17 β-Hydroxy-Androstanes
2.3. Correlation Between Indices of MS Severity and Steroids
2.3.1. Expanded Disability Status Scale (EDSS)
Variable | OPLS, Predictive Component | Multiple Regression | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | ||||||
Explaining Variables | Pregnenolone | 1.35 | 4.77 | ** | −0.304 | −4.50 | −0.640 | ** | −2.64 | * | |
17-Hydroxypregnenolone | 1.075 | 2.16 | * | −0.310 | −3.29 | −0.654 | ** | −2.09 | * | ||
7α-Hydroxy-DHEA | 0.667 | 2.43 | * | −0.379 | −8.87 | −0.798 | ** | −1.78 | |||
5-Androstene-3β,7α,17β-triol | 0.79 | 3.18 | ** | −0.380 | −6.39 | −0.800 | ** | −1.88 | |||
5-Androstene-3β,7β,17β-triol | 0.93 | 2.91 | * | −0.366 | −8.15 | −0.772 | ** | −1.67 | |||
17,20α-Dihydroxy-4-pregnene-3-one | 0.889 | 2.04 | * | −0.316 | −7.71 | −0.667 | ** | −1.69 | |||
Androstenedione | 1.317 | 4.40 | ** | −0.371 | −7.08 | −0.783 | ** | −5.34 | ** | ||
5β-Pregnane-3α,17,20α-triol | 0.73 | 3.70 | ** | −0.334 | −7.22 | −0.703 | ** | −1.92 | * | ||
Androsterone | 1.093 | 1.94 | * | −0.210 | −3.15 | −0.443 | ** | −1.60 | |||
11β-Hydroxyandrostenedione | 0.915 | 3.13 | ** | −0.308 | −13.16 | −0.649 | ** | −2.95 | * | ||
Explained Variable | Expanded Disability Status Scale | 1.000 | 2.52 | 0.388 | * | ||||||
Follicular phase | R2 = 15.1%, Q2 = 8.4%, CV-ANOVA: F = 2.03, p = 0.144 |
Variable | OPLS, Predictive Component | Multiple Regression | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | ||||||
Explaining Variables | Dehydroepiandrosterone | 0.645 | 2.24 | * | 0.145 | 1.06 | 0.180 | 1.58 | |||
5α,20α-Tetrahydroprogesterone | 0.816 | 2.26 | * | 0.458 | 2.83 | 0.566 | * | 1.38 | |||
5β-Pregnane-3α,20α-diol | 1.053 | 3.91 | ** | 0.455 | 3.41 | 0.562 | ** | 1.93 | * | ||
5β-Androstane-3α,17β-diol | 1.092 | 2.73 | * | −0.574 | −2.33 | −0.709 | * | −1.98 | * | ||
11β-Hydroxyandrostenedione | 1.271 | 3.33 | ** | −0.521 | −1.87 | −0.644 | −2.35 | * | |||
Explained Variable | Expanded Disability Status Scale | 1.000 | 5.09 | 0.710 | ** | ||||||
Luteal phase | R2 = 50.3%, Q2 = 24.4%, CV-ANOVA: F = 1.93, p = 0.187 |
2.3.2. Timed 25-Foot Walk (T25-FW)
Variable | OPLS, Predictive Component | Multiple Regression | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | ||||||
Explaining Variables | Age | 0.915 | 2.27 | * | 0.146 | 1.71 | 0.342 | 1.99 | * | ||
Pregnenolone | 0.671 | 2.62 | * | −0.100 | −0.96 | −0.233 | −2.22 | * | |||
17-Hydroxypregnenolone | 0.873 | 2.98 | * | −0.214 | −4.58 | −0.502 | ** | −2.39 | * | ||
16α-Hydroxypregnenolone | 1.171 | 3.83 | ** | −0.200 | −3.66 | −0.469 | ** | −2.57 | * | ||
Dehydroepiandrosterone | 0.67 | 2.71 | * | −0.167 | −2.59 | −0.390 | * | −1.94 | * | ||
16α-Hydroxyprogesterone | 0.615 | 2.11 | * | −0.148 | −1.59 | −0.345 | −2.19 | * | |||
Allopregnanolone, C | 1.517 | 4.96 | ** | 0.310 | 5.45 | 0.726 | ** | 4.75 | ** | ||
Isopregnanolone, C | 1.587 | 5.08 | ** | 0.321 | 4.86 | 0.751 | ** | 3.57 | ** | ||
Pregnanolone, C | 1.241 | 6.39 | ** | 0.339 | 8.33 | 0.793 | ** | 4.93 | ** | ||
5β-Pregnane-3α,20α-diol, C | 0.682 | 2.63 | * | 0.225 | 1.96 | 0.528 | * | 2.91 | * | ||
Androsterone, C | 0.825 | 3.24 | ** | 0.273 | 4.16 | 0.638 | ** | 3.87 | ** | ||
Epiandrosterone, C | 1.167 | 4.22 | ** | 0.278 | 6.34 | 0.651 | ** | 2.78 | * | ||
Etiocholanolone, C | 0.804 | 2.42 | * | 0.278 | 5.23 | 0.650 | ** | 3.17 | ** | ||
Epietiocholanolone, C | 1.047 | 3.28 | ** | 0.339 | 5.91 | 0.793 | ** | 3.45 | ** | ||
5α-Androstane-3β,17β-diol, C | 0.956 | 5.92 | ** | 0.287 | 9.13 | 0.671 | ** | 5.36 | ** | ||
11β-Hydroxyandrosterone | 0.674 | 2.68 | * | 0.125 | 1.81 | 0.294 | 1.90 | * | |||
11β-Hydroxyandrosterone, C | 1.057 | 5.26 | ** | 0.242 | 6.55 | 0.566 | ** | 3.00 | ** | ||
11β-Hydroxyepiandrosterone | 0.812 | 2.29 | * | 0.150 | 1.81 | 0.351 | 1.92 | * | |||
Explained Variable | Timed 25-Foot Walk | 1.000 | 11.44 | 0.726 | ** | ||||||
Follicular phase | R2 = 46.8%, Q2 = 28.8%, CV-ANOVA: F = 11.7, p < 0.001 |
Variable | OPLS, Predictive Component | Multiple Regression | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | ||||||
Explaining Variables | Age | 1.162 | 1.98 | * | −0.233 | −0.80 | −0.391 | −1.69 | |||
Androstenediol | 1.117 | 3.35 | ** | −0.362 | −2.31 | −0.609 | * | −2.98 | * | ||
5-Androstene-3β,7α,17β-triol | 0.899 | 2.83 | * | −0.412 | −1.90 | −0.693 | * | −4.13 | ** | ||
5-Androstene-3β,7β,17β-triol | 0.828 | 2.08 | * | −0.374 | −1.49 | −0.629 | −3.08 | ** | |||
16α-Hydroxyprogesterone | 0.932 | 6.41 | ** | −0.388 | −3.14 | −0.652 | ** | −2.74 | * | ||
Androstenedione | 1.021 | 1.95 | * | −0.401 | −3.63 | −0.675 | ** | −1.66 | |||
5α,20α-Tetrahydroprogesterone | 0.955 | 2.48 | * | −0.237 | −1.27 | −0.398 | −1.90 | * | |||
11β-Hydroxyandrostenedione | 1.096 | 3.86 | ** | −0.349 | −3.87 | −0.586 | ** | −2.93 | * | ||
11β-Hydroxyandrosterone | 0.941 | 2.97 | * | −0.282 | −1.13 | −0.475 | −2.06 | * | |||
Explained Variable | Timed 25-Foot Walk | 1.000 | 8.57 | 0.783 | ** | ||||||
Luteal phase | R2 = 61.3% Q2 = 49.8%, CV-ANOVA: F = 4.97, p = 0.031 |
2.3.3. 9-Hole Peg Test (9-HPT) for MS, Right Hand
OPLS, Predictive Component | Multiple Regression | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable | Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | |||||
Explaining Variables | Pregnenolone | 1.115 | 5.77 | ** | −0.496 | −5.14 | −0.697 | ** | −2.76 | * | |
16α-Hydroxypregnenolone | 1.130 | 4.70 | ** | −0.581 | −10.20 | −0.817 | ** | −3.55 | ** | ||
Dehydroepiandrosterone | 0.948 | 2.61 | * | −0.507 | −7.70 | −0.713 | ** | −2.67 | * | ||
Androsterone | 0.763 | 3.21 | ** | −0.407 | −4.22 | −0.572 | ** | −3.62 | ** | ||
Explained Variable | 9-Hole Peg Test, right hand | 1.000 | 2.01 | 0.517 | * | ||||||
Follicular phase | R2 = 26.7%, Q2 = 21.2%, CV-ANOVA: F = 3.64, p = 0.040 |
Variable | OPLS, Predictive Component | Multiple Regression | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | ||||||
Explaining Variables | 17-Hydroxypregnenolone, C | 0.944 | 3.78 | ** | −0.265 | −4.36 | −0.426 | ** | −0.58 | ||
16α-Hydroxypregnenolone | 0.474 | 2.07 | * | −0.102 | −0.98 | −0.164 | 1.91 | * | |||
Dehydroepiandrosterone | 0.648 | 2.00 | * | −0.198 | −1.46 | −0.318 | 0.35 | ||||
Dehydroepiandrosterone, C | 1.029 | 5.95 | ** | −0.290 | −4.28 | −0.466 | ** | −2.04 | * | ||
5-Androstene-3β,16α,17β-triol, C | 0.963 | 3.22 | ** | −0.269 | −2.30 | −0.432 | * | −1.63 | |||
Androstenedione | 0.741 | 2.06 | * | 0.241 | 1.91 | 0.387 | * | 2.62 | * | ||
5α,20α-Tetrahydroprogesterone | 1.26 | 2.49 | * | 0.380 | 2.47 | 0.611 | * | 1.41 | |||
Androsterone, C | 0.933 | 2.82 | * | −0.288 | −3.70 | −0.463 | ** | −0.62 | |||
Etiocholanolone, C | 0.855 | 3.97 | ** | −0.233 | −4.46 | −0.374 | ** | −0.80 | |||
Epietiocholanolone, C | 0.734 | 2.24 | * | −0.271 | −1.87 | −0.435 | 0.19 | ||||
5α-Androstane-3β,17β-diol, C | 1.206 | 5.99 | ** | −0.361 | −2.84 | −0.579 | * | −1.81 | |||
11β-Hydroxyandrosterone, C | 1.657 | 12.51 | ** | −0.435 | −5.35 | −0.698 | ** | −1.99 | * | ||
Explained Variable | 9-Hole Peg Test, right hand | 1.000 | 3.78 | 0.825 | ** | ||||||
Luteal phase | R2 = 68.1%, Q2 = 34.8%, CV-ANOVA: F = 1.07, p = 0.432 |
2.3.4. 9-Hole Peg Test (9-HPT) for MS, Left Hand
Variable | OPLS, Predictive Component | Multiple Regression | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | ||||||
Explaining Variables | Pregnenolone | 1.267 | 2.99 | * | −0.547 | −3.23 | −0.733 | ** | −2.14 | * | |
5-Androstene-3β,16α,17β-triol, C | 1.158 | 2.49 | * | 0.469 | 2.45 | 0.629 | * | 2.30 | * | ||
5α,20α-Tetrahydroprogesterone | 0.774 | 2.02 | * | −0.320 | −1.52 | −0.429 | −1.05 | ||||
5α-Pregnane-3α,20α-diol, C | 0.65 | 2.01 | * | −0.219 | −1.76 | −0.293 | −1.00 | ||||
Androsterone, C | 1.067 | 3.18 | ** | −0.390 | −2.68 | −0.523 | * | −1.32 | |||
5α-Androstane-3α,17β-diol, C | 0.946 | 2.66 | * | −0.431 | −2.87 | −0.578 | * | −0.89 | |||
Explained Variable | 9-Hole Peg Test, left hand | 1.000 | 2.86 | 0.608 | * | ||||||
Follicular phase | R2 = 37.0%, Q2 = 23.3%, CV-ANOVA: F = 2.12, p = 0.104 |
Variable | OPLS, Predictive Component | Multiple Regression | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Variable Importance | t-Statistic | Component Loading | t-Statistic | R | t-Statistic | ||||||
Explaining Variables | 5-Androstene-3β,16α,17β-triol, C | 1.024 | 3.22 | ** | −0.595 | −2.27 | −0.712 | * | −3.29 | ** | |
11β-Hydroxyandrostenedione | 0.64 | 1.95 | * | −0.412 | −1.67 | −0.493 | −1.94 | * | |||
11β-Hydroxyandrosterone, C | 1.19 | 3.28 | ** | −0.466 | −1.22 | −0.557 | −3.45 | ** | |||
11β-Hydroxyepiandrosterone | 1.061 | 2.57 | * | −0.540 | −1.69 | −0.646 | −2.40 | * | |||
Explained Variable | 9-Hole Peg Test, left hand | 1.000 | 4.86 | 0.824 | ** | ||||||
Luteal phase | R2 = 67.9%, Q2 = 63.7%, CV-ANOVA: F = 7.90, p = 0.010 |
3. Discussion
3.1. Correlations Between Steroids in Serum and Cerebrospinal Fluid
3.2. Alterations in Steroid Levels
3.2.1. Δ5 and Δ4 Steroids
3.2.2. 11β-. Hydroxy-Androstanes (C19 Δ4 and 5α/β Steroids)
3.2.3. GABAergic Steroids
3.2.4. 17-oxo- and 17 β-Hydroxy-Androstanes
3.3. Correlation Between Indices of MS Severity and Steroids
4. Potential Clinical Implications of the Findings
5. Future Directions
6. Limitations and Strengths of the Study
7. Materials and Methods
7.1. Subjects
7.2. Steroid Analysis
7.3. Statistical Analysis
8. Conclusions
- (1)
- Both unconjugated and conjugated steroids exhibited a strong correlation between the circulation and CSF, suggesting steroid transfer from the bloodstream to the CNS and underscoring the significance of peripheral steroidogenesis.
- (2)
- The noticeable decrease in unconjugated steroid levels implies diminished steroidogenesis in MS patients compared to controls. In contrast, the absence of significant changes in conjugated steroids could indicate heightened functioning of sulfotransferase (SULT2A1) in these patients.
- (3)
- Reduced functioning of adrenal 11β-hydroxylase (CYP11B1), essential for the final step of cortisol synthesis, has been observed in MS patients. Additionally, impaired cortisol metabolism, involving decreased CYP17A1 and CYP11B1 functioning, was associated with more severe 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)
- The steroidomic data indicates that higher AKR1C3 functioning in MS patients might cause inflammation, as this enzyme is involved in the production of both steroids and prostaglandins.
- (6)
- Reduced pregnenolone levels in MS patients could weaken protection against demyelination, whereas elevated pregnenolone sulfate levels in this group might help safeguard against cognitive deficits.
- (7)
- MS severity was inversely associated with neuroprotective pregnenolone, its sulfate, DHEA, its sulfate, and immunomodulatory steroids such as androstenediol and its hydroxy-metabolites, highlighting their potentially protective role in MS.
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Steroid | r | p-Value | Steroid | r | p-Value | |
---|---|---|---|---|---|---|
Pregnenolone | 0.303 | 0.002 | 5α,20α-Tetrahydroprogesterone | 0.499 | <0.001 | |
Pregnenolone sulphate | 0.315 | <0.001 | Conjugated 5α-pregnane-3α,20α-diol | 0.492 | <0.001 | |
17-Hydroxypregnenolone | 0.641 | <0.001 | Conjugated 5α-pregnane-3β,20α-diol | 0.727 | <0.001 | |
16α-Hydroxypregnenolone | 0.632 | <0.001 | Conjugated 5β-pregnane-3α,20α-diol | 0.428 | <0.001 | |
20α-Dihydropregnenolone sulphate | 0.473 | <0.001 | Conjugated 5β-pregnane-3β,20α-diol | 0.61 | <0.001 | |
Dehydroepiandrosterone (DHEA) | 0.479 | <0.001 | 5α-Pregnane-3α,17,20α-triol | 0.499 | <0.001 | |
DHEA sulphate | 0.692 | <0.001 | 5β-Pregnane-3α,17,20α-triol | 0.723 | <0.001 | |
7α-Hydroxy-DHEA | 0.63 | <0.001 | Androsterone | 0.477 | <0.001 | |
7β-Hydroxy-DHEA | 0.749 | <0.001 | Androsterone sulphate | 0.488 | <0.001 | |
Androstenediol | 0.28 | 0.003 | Epiandrosterone sulphate | 0.38 | <0.001 | |
Androstenediol sulphate | 0.561 | <0.001 | Etiocholanolone sulphate | 0.453 | <0.001 | |
5-Androstene-3β,7α,17β-triol | 0.662 | <0.001 | Epietiocholanolone sulphate | 0.5 | <0.001 | |
5-Androstene-3β,7β,17β-triol | 0.567 | <0.001 | Conjugated 5α-androstane-3α,17β-diol | 0.512 | <0.001 | |
5-Androstene-3β,16α,17β-triol sulphate | 0.644 | <0.001 | Conjugated 5α-androstane-3β,17β-diol | 0.698 | <0.001 | |
17,20α-Dihydroxy-4-pregnene-3-one | 0.418 | <0.001 | Conjugated 5β-androstane-3α,17β-diol | 0.33 | <0.001 | |
16α-Hydroxyprogesterone | 0.801 | <0.001 | 11β-Hydroxyandrostenedione | 0.205 | 0.058 | |
Androstenedione | 0.412 | <0.001 | 11β-Hydroxyandrosterone | 0.771 | <0.001 | |
Conjugated pregnanolone | 0.688 | <0.001 | 11β-Hydroxyetiocholanolone sulphate | 0.878 | <0.001 |
ANOVA, p-Values | Trend MS+, (p < 0.05) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Steroid | Follicular, MS− | Follicular, MS+ | Luteal, MS− | Luteal, MS+ | MS | PMC | MS×PMC | Age | Factor MS | MC, FP | OPLS, FP | MC, LP | OPLS, LP | Trend | |
Pregnenolone [pM] | 32.9 (26, 41.7) | 19.4 (16.7, 22.5) | 17.5 (13.1, 23.4) | 15.7 (12, 20.5) | 0.066 | 0.016 | 0.224 | 0.380 | ↓ | ↓ | |||||
Pregnenolone sulphate [pM] | 94.3 (74, 121) | 108 (91.1, 128) | 80.6 (60.6, 108) | 220 (154, 321) | 0.004 | 0.177 | 0.029 | 0.009 | ↑ | ↑ | ↑ | ||||
17-Hydroxypregnenolone [pM] | 31 (23.1, 41.7) | 42.2 (34.7, 51.3) | 41.6 (29.2, 59.4) | 27.3 (19.6, 37.9) | 0.787 | 0.741 | 0.091 | 0.401 | |||||||
16α-Hydroxypregnenolone [pM] | 6.41 (4.81, 8.55) | 3.1 (2.61, 3.68) | 4.07 (2.98, 5.57) | 2.3 (1.69, 3.11) | 0.001 | 0.057 | 0.693 | 0.193 | ↓ | ↓ | ↓ | ↓ | ↓ | ||
20α-Dihydropregnenolone sulphate [pM] | 320 (259, 395) | 350 (304, 402) | 402 (308, 525) | 450 (348, 583) | 0.533 | 0.137 | 0.941 | 0.658 | |||||||
Dehydroepiandrosterone (DHEA) [pM] | 143 (111, 184) | 117 (98.7, 138) | 111 (81.5, 151) | 108 (80, 146) | 0.539 | 0.383 | 0.642 | 0.154 | |||||||
DHEA sulphate [nM] | 0.571 (0.454, 0.715) | 0.634 (0.545, 0.736) | 0.82 (0.624, 1.08) | 1.25 (0.93, 1.69) | 0.130 | 0.003 | 0.351 | 0.829 | |||||||
7α-Hydroxy-DHEA [nM] | 0.328 (0.269, 0.396) | 0.841 (0.766, 0.922) | 0.474 (0.386, 0.577) | 0.897 (0.747, 1.07) | 0.000 | 0.092 | 0.263 | 0.009 | ↑ | ↑ | ↑ | ↑ | |||
7β-Hydroxy-DHEA [pM] | 86.8 (66.8, 111) | 81.9 (69.1, 96.3) | 63.3 (45.5, 85.5) | 45.6 (31.7, 63.3) | 0.342 | 0.023 | 0.529 | 0.236 | |||||||
Androstenediol [pM] | 12.2 (9.71, 15.1) | 10.3 (8.76, 12.1) | 12.1 (9.03, 15.8) | 16.1 (12.8, 20) | 0.672 | 0.175 | 0.162 | 0.849 | ↓ | ↓ | |||||
Androstenediol sulphate [nM] | 1.23 (1.03, 1.47) | 1.39 (1.23, 1.56) | 1 (0.801, 1.25) | 2.56 (2.06, 3.18) | 0.000 | 0.114 | 0.003 | 0.052 | ↑ | ↑ | ↑ | ||||
5-Androstene-3β,7α,17β-triol [pM] | 110 (83.5, 143) | 111 (93, 131) | 82.3 (58.5, 114) | 129 (94.5, 175) | 0.249 | 0.741 | 0.267 | 0.428 | |||||||
5-Androstene-3β,7β,17β-triol [pM] | 35.5 (27.9, 45.2) | 32.1 (27.3, 37.8) | 32.4 (24, 43.7) | 34.5 (25.8, 46) | 0.920 | 0.955 | 0.657 | 0.060 | |||||||
5-Androstene-3β,16α,17β-triol sulphate [pM] | 72.1 (57.3, 90.4) | 31.4 (26.8, 36.6) | 45.4 (33.7, 60.6) | 23 (16.8, 31) | 0.000 | 0.032 | 0.604 | 0.007 | ↓ | ↓ | ↓ | ↓ | |||
17,20α-Dihydroxy-4-pregnene-3-one [pM] | 11.8 (9.52, 14.6) | 15.2 (13.2, 17.6) | 41.6 (32.7, 52.7) | 16.6 (12.7, 21.4) | 0.024 | 0.000 | 0.000 | 0.048 | ↓ | ↓ | ↓ | ↓ | |||
16α-Hydroxyprogesterone [pM] | 9.45 (6.83, 12.9) | 15.3 (12.6, 18.5) | 60.1 (43.8, 82.1) | 48.9 (35.5, 66.9) | 0.575 | 0.000 | 0.111 | 0.017 | ↓ | ↓ | |||||
Androstenedione [pM] | 75.5 (65, 87.4) | 73.4 (67.1, 80.2) | 83 (70.9, 96.7) | 111 (94.8, 129) | 0.182 | 0.012 | 0.109 | 0.000 | ↓ | ↓ | |||||
Conjugated pregnanolone [pM] | 63.5 (52.4, 76.2) | 68.5 (59.9, 78) | 143 (118, 171) | 137 (112, 167) | 0.930 | 0.000 | 0.661 | 0.238 | |||||||
5α,20α-Tetrahydroprogesterone [pM] | 3.62 (2.76, 4.77) | 2.73 (2.33, 3.21) | 9.08 (6.59, 12.7) | 6.56 (4.87, 8.95) | 0.118 | 0.000 | 0.974 | 0.047 | ↓ | ↓ | |||||
Conjugated 5α-pregnane-3α,20α-diol [pM] | 162 (133, 198) | 96.1 (84.7, 109) | 393 (296, 525) | 330 (260, 422) | 0.025 | 0.000 | 0.236 | 0.092 | ↓ | ↓ | ↓ | ||||
Conjugated 5α-pregnane-3β,20α-diol [pM] | 66.5 (42.3, 106) | 36.6 (26.7, 50.1) | 91.5 (52.3, 164) | 323 (176, 620) | 0.409 | 0.001 | 0.011 | 0.044 | ↑ | ↑ | |||||
Conjugated 5β-pregnane-3α,20α-diol [pM] | 54.3 (43.6, 67.2) | 73.5 (63.5, 85) | 168 (130, 219) | 222 (171, 289) | 0.077 | 0.000 | 0.951 | 0.010 | |||||||
Conjugated 5β-pregnane-3β,20α-diol [pM] | 53.7 (45.5, 63.3) | 63.3 (56.6, 70.7) | 105 (85.8, 128) | 78.2 (63.9, 95.8) | 0.621 | 0.001 | 0.068 | 0.049 | |||||||
5α-Pregnane-3α,17,20α-triol [pM] | 0.534 (0.391, 0.74) | 0.38 (0.312, 0.465) | 0.634 (0.424, 0.974) | 0.502 (0.354, 0.726) | 0.222 | 0.337 | 0.804 | 0.006 | ↓ | ↓ | ↓ | ||||
5β-Pregnane-3α,17,20α-triol [pM] | 18.1 (14.9, 21.8) | 25.6 (22.8, 28.7) | 39.5 (33, 46.9) | 22.8 (18.5, 28) | 0.343 | 0.008 | 0.001 | 0.167 | ↑ | ↓ | |||||
Androsterone [pM] | 29.5 (25, 34.9) | 18.8 (17, 20.7) | 47.8 (39.2, 58.8) | 6.73 (5.38, 8.37) | 0.000 | 0.015 | 0.000 | 0.071 | ↓ | ↓ | ↓ | ↓ | ↓ | ||
Androsterone sulphate [pM] | 460 (381, 559) | 307 (271, 347) | 363 (292, 455) | 292 (236, 363) | 0.025 | 0.307 | 0.512 | 0.005 | ↓ | ↓ | ↓ | ||||
Epiandrosterone sulphate [pM] | 151 (119, 189) | 180 (155, 208) | 170 (127, 225) | 158 (116, 211) | 0.775 | 0.982 | 0.473 | 0.324 | |||||||
Etiocholanolone sulphate [pM] | 132 (112, 155) | 126 (113, 140) | 126 (104, 153) | 116 (94, 144) | 0.620 | 0.617 | 0.889 | 0.520 | ↓ | ↓ | |||||
Epietiocholanolone sulphate [pM] | 47.3 (38.3, 58.1) | 60.9 (52.6, 70.4) | 42.3 (32.8, 54.3) | 41.8 (31.7, 54.4) | 0.443 | 0.125 | 0.395 | 0.857 | ↓ | ↓ | |||||
Conjugated 5α-androstane-3α,17β-diol [pM] | 532 (422, 673) | 405 (349, 472) | 333 (252, 441) | 337 (255, 447) | 0.459 | 0.062 | 0.420 | 0.069 | ↑ | ↑ | |||||
Conjugated 5α-androstane-3β,17β-diol [pM] | 143 (112, 182) | 108 (91.1, 128) | 106 (77.4, 142) | 108 (78.3, 146) | 0.481 | 0.402 | 0.419 | 0.845 | |||||||
Conjugated 5β-androstane-3α,17β-diol [pM] | 18.9 (15.2, 23.4) | 20.3 (17.5, 23.5) | 30.9 (23.4, 40.7) | 23.7 (18.2, 30.7) | 0.557 | 0.052 | 0.299 | 0.645 | |||||||
11β-Hydroxyandrostenedione [nM] | 2.09 (1.87, 2.33) | 1.82 (1.69, 1.96) | 2.35 (2.07, 2.65) | 1.9 (1.67, 2.15) | 0.030 | 0.321 | 0.614 | 0.087 | ↓ | ↓ | |||||
11β-Hydroxyandrosterone [pM] | 182 (147, 225) | 91.1 (77.2, 107) | 131 (98.9, 171) | 82.4 (61.3, 109) | 0.001 | 0.196 | 0.459 | 0.001 | ↓ | ↓ | ↓ | ↓ | ↓ | ||
11β-Hydroxyandrosterone sulphate [pM] | 116 (105, 128) | 110 (102, 119) | 137 (119, 157) | 93.6 (82, 106) | 0.009 | 0.890 | 0.044 | 0.881 | ↓ | ↓ | ↓ | ||||
11β-Hydroxyetiocholanolone [pM] | 75.4 (61.2, 91.8) | 66.9 (58.1, 76.8) | 84.4 (67.8, 104) | 62.5 (49.3, 78.2) | 0.143 | 0.864 | 0.522 | 0.001 | ↓ | ↓ | ↓ | ||||
11β-Hydroxyetiocholanolone sulphate [pM] | 149 (120, 182) | 191 (166, 218) | 233 (186, 289) | 193 (152, 242) | 0.860 | 0.115 | 0.137 | 0.917 |
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Kancheva, R.; Kubala Havrdová, E.; Velíková, M.; Kancheva, L.; Včelák, J.; Ampapa, R.; Židó, M.; Štětkářová, I.; Škodová, T.; Hill, M. Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis. Int. J. Mol. Sci. 2025, 26, 5904. https://doi.org/10.3390/ijms26125904
Kancheva R, Kubala Havrdová E, Velíková M, Kancheva L, Včelák J, Ampapa R, Židó M, Štětkářová I, Škodová T, Hill M. Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis. International Journal of Molecular Sciences. 2025; 26(12):5904. https://doi.org/10.3390/ijms26125904
Chicago/Turabian StyleKancheva, Radmila, Eva Kubala Havrdová, Marta Velíková, Ludmila Kancheva, Josef Včelák, Radek Ampapa, Michal Židó, Ivana Štětkářová, Tereza Škodová, and Martin Hill. 2025. "Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis" International Journal of Molecular Sciences 26, no. 12: 5904. https://doi.org/10.3390/ijms26125904
APA StyleKancheva, R., Kubala Havrdová, E., Velíková, M., Kancheva, L., Včelák, J., Ampapa, R., Židó, M., Štětkářová, I., Škodová, T., & Hill, M. (2025). Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis. International Journal of Molecular Sciences, 26(12), 5904. https://doi.org/10.3390/ijms26125904